(Stroke. 2000;31:961.)
© 2000 American Heart Association, Inc.
Original Contributions |
Regional Cerebral Blood Flow After Cortical Impact Injury Complicated by a Secondary Insult in Rats
From the Departments of Neurosurgery (B.K.G., I.K.K., C.R.) and Anesthesiology (R.M.B.), Baylor College of Medicine, Houston, Tex.
Correspondence to Claudia Robertson, MD, Department of Neurosurgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail claudiar{at}bcm.tmc.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferencesIntroduction |
|---|
Background and Purpose—Traumatic injury makes the brain susceptible to secondary insults. An uncomplicated mild lateral cortical impact injury (3 m/s, 2.5-mm deformation) that causes little or no permanent sequelae results in a large contusion at the impact site when the traumatic injury is complicated by a secondary insult, such as 40 minutes of bilateral carotid occlusion.
Methods—To determine whether the increased sensitivity to secondary insults in this model is caused by a vascular mechanism, cerebral blood flow (CBF) was measured with 14C-isopropyliodoamphetamine quantitative autoradiography, and brain tissue PO2 (PbtO2) was measured at the impact site and in the contralateral parietal cortex.
Results—In animals that underwent bilateral carotid occlusion 1 hour after the impact injury, CBF and PbtO2 were lower at the impact site than they were in animals that had either the impact injury or the carotid occlusion alone. In the immediate area of the impact, CBF was 14±6 mL · 100 g-1 · min-1 in the animals with the impact injury followed by carotid occlusion compared with 53±24 mL · 100 g-1 · min-1 in the animals with the impact injury alone and 74±14 mL · 100 g-1 · min-1 in the animals with the carotid occlusion alone (P<0.001). At the time of this very low CBF value in the animals with the carotid occlusion after the impact injury, PbtO2 at the impact site averaged 1.3±1.6 mm Hg and was <3 mm Hg in 5 of the 6 animals. In contrast, PbtO2 in the animals with the impact injury alone averaged 9.3±2.9 mm Hg, and none of the animals had a PbtO2 of <3 mm Hg (P=0.008).
Conclusions—The CBF and PbtO2 findings in this model suggest that the reduced CBF after traumatic injury predisposes the brain to secondary insults and results in ischemia when confronted with a reduction in cerebral perfusion pressure.
Key Words: brain injuries • cerebral blood flow • cerebral ischemia • trauma
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferencesIntroduction |
|---|
Secondary ischemic insults are an important cause of damage to the brain after traumatic brain injury (TBI). In a number of clinical studies, a poor outcome has consistently been associated with prehospital hypotension or hypoxia,1 2 3 4 5 6 with intraoperative hypotension,7 and with hypoxia and hypotension in the intensive care unit.2 8 9 10
In the laboratory, a mild lateral cortical impact injury (3 m/s, 2.5-mm deformation) that causes little or no permanent sequelae results in a large contusion at the impact site when the traumatic injury is complicated by 40 minutes of bilateral carotid occlusion (BCO).11 A similar sensitivity to secondary insults has been observed in the fluid percussion injury model12 13 14 and the weight-drop model.15
Two general mechanisms may be responsible for the increased sensitivity of the traumatized brain to ischemic insults.16 First, it is likely that trauma impairs the ability of the brain to regulate cerebral blood flow (CBF), and for any given insult, the cerebrovascular response after TBI may be inadequate. In many studies, both clinical and experimental, impaired autoregulation has been observed after TBI.17 18 19 20 21 22 Second, trauma may induce cellular processes that make the brain more sensitive to an additional insult. This mechanism is supported by studies in which the CBF response is similar in the trauma and the nontrauma animals12 and by in vitro studies in which CBF is not a factor.23
To determine whether the vascular mechanism is a factor in the cortical impact injury model, regional CBF (rCBF) was measured with quantitative autoradiography in a group of animals that underwent a 3-m/s impact injury followed 1 hour later by 40 minutes of carotid occlusion. The measurement of reduced CBF does not necessarily indicate oxygen depletion and, therefore, ischemia. Because reduced CBF associated with TBI may be simply a manifestation of a reduced metabolic rate, brain tissue PO2 (PbtO2) was measured continuously during the uncomplicated cortical impact injury and during the cortical impact injury followed by 40 minutes of BCO.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferencesIntroduction |
|---|
Male Long Evans rats that weighed approximately 350 g and were fasted overnight were used in the experiments: 15 for the measurement of CBF and 12 for the measurement of PbtO2. The protocol for this study was approved by the Animal Protocol Review Committee of Baylor College of Medicine. For both experiments, the rats were anesthetized with 3.5% isoflurane in 100% oxygen in a vented anesthesia chamber. After endotracheal intubation with a 16-gauge Teflon catheter, the rats were mechanically ventilated with 2% to 3% isoflurane in 100% oxygen for the remainder of the experiment. Rectal temperature was monitored and maintained at 37°C with a heating pad. The ventilator was adjusted to maintain arterial PCO2 near 35 mm Hg.
For both studies, a catheter was placed in the left femoral artery to monitor blood pressure and to draw blood samples. Arterial blood was periodically sampled and analyzed for PO2, PCO2, and pH. For the measurement of CBF, catheters were also inserted into the right femoral artery and vein.
Both carotid arteries were exposed via a vertical midline incision and carefully dissected free from the other contents of the carotid sheath. The head of each rat was fixed in a stereotaxic frame with ear bars, and a 10-mm-diameter craniectomy was performed in the right parietal skull adjacent to the midline in preparation for the cortical impact injury. The dura was left intact. For the PbtO2 experiment, a Clark electrode PO2 catheter and thermacouple temperature probe (Licox PO2 catheter and thermacouple catheter; GMS) were placed into the brain parenchyma at the exposed impact site and in the contralateral parietal lobe via a small burr hole. The PO2 catheter was calibrated before insertion, and the calibration was checked again at the end of the experiment. The PO2 values were temperature corrected to the brain temperature indicated by the adjacent thermacouple catheter.
The animals were randomly assigned to 1 of 3 treatment groups: (1) TBI+BCO group (3 m/s, 2.5-mm deformation impact injury, followed 1 hour later by 40 minutes of BCO), and (2) TBI group (3 m/s, 2.5-mm deformation impact injury, followed 1 hour later by 40 minutes of sham carotid occlusion), and (3) BCO group (sham impact injury, followed 1 hour later by 40 minutes of BCO).
In 15 of the animals (5 in each of the 3 treatment groups), CBF was
measured at the end of the 40-minute BCO or sham carotid occlusion
period. CBF was measured with
14C-isopropyliodoam-phetamine (IPIA) and
quantitative autoradiography.24 IPIA is
useful as a flow tracer because it is extracted 100% in the brain
during a single pass.25 The IPIA (29 µCi/mmol) was
custom synthesized at Du Pont-New England Nuclear. IPIA (50 µCi/0.5
mL) in normal saline was injected quickly into the right femoral vein.
Blood was withdrawn from the right femoral artery at a rate of 0.4
mL/min beginning at the time of IPIA infusion and continuing until the
rat was sacrificed 30 seconds later with the use of a guillotine. After
death, the brain was rapidly removed, frozen in isoheptane chilled to
-40°C, and stored at -70°C until it was sectioned. Each brain was
cut into 20-µm-thick sections with a cryostat (-18°C).
Representative sections were mounted onto glass slides
and placed in contact with radiograph film in light-tight cassettes.
After a 15-day exposure, the film was developed, producing
autoradiographic images. Concentrations of the tracer
(radioactivity/g brain tissue) were determined by comparing the optical
densities of various brain regions with the optical densities produced
with calibrated standards packed with tissue sections in the cassettes.
The total radioactivity in the blood withdrawn was calculated according
to the following equation:
 |
 |
In 12 animals (6 randomized to the TBI+BCO group and 6 randomized to the TBI group), PbtO2 was measured before the impact injury, with 45 minutes allowed for the catheter readings to stabilize. The catheter at the impact site was removed for the impact injury and then immediately replaced into the same area of the brain. PbtO2 was then monitored after the impact injury for 3 hours. The PbtO2 on the injured side was compared with the values obtained for the contralateral uninjured side of the brain.
Data are reported for all groups as mean±SD. Analyses of CBF data were performed with 2-way ANOVA with treatment group and side of the brain as factors. The PbtO2 data were analyzed with repeated measures ANOVA with time and side of the brain as factors. Tukey’s test was used for multiple comparisons, and Fisher’s exact test was used for categorical data.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferencesIntroduction |
|---|
CBF Measurements
Physiological measurements, including mean blood pressure, arterial pH, PCO2, and PO2, were made in each rat before injury and are presented in Table 1
. There were no significant
differences in the physiological measurements among
the 3 groups. Arterial
PCO2 in the TBI+BCO group, which
tended to be slightly lower than that in the other 2 groups at
baseline, was normalized during the experiment and averaged 35±3
mm Hg, a value similar to that of the other groups at the time of the
CBF measurement.
|
Representative examples of the autoradiographs for the
3 experimental groups are shown in Figure 1. A summary of all of the CBF data is
given in Table 2.
|
|
In the animals that underwent only the impact injury (TBI group),
CBF tended to be less on the impacted right side in all of the cortical
areas (frontal, parietal, temporal, occipital) and in the hippocampus.
However, these right–left differences were significant only in the
parietal cortex (motor area), in the occipital cortex (areas A18 and
A18a), and in the hippocampus (Table 2
). CBF was reduced to
54±24 and 42±33 mL · 100 g-1 ·
min-1 in the parietal cortex (motor area) and in
the occipital cortex, respectively, on the impacted side. In the
hippocampus, CBF was 254±33 mL · 100
g-1 · min-1 on the
impacted side compared with 319±44 mL · 100
g-1 · min-1 on the
uninjured side. In the remainder of the brain regions, there were no
significant differences in CBF between the right and left sides after
adjustment for multiple comparisons with Tukey’s method.
In the animals that underwent only the BCO (BCO group), CBF was
moderately reduced in the forebrain on both sides. Regions in the
hindbrain were less affected. There were no significant right–left
differences in CBF in any areas of the brain (Table 2). CBF was
not reduced to ischemic levels in any area of the brain.
In the animals that underwent BCO 1 hour after the impact injury
(TBI+BCO group), CBF was significantly lower than that in either the
TBI group or the BCO group at the impact site. In the immediate area of
the impact, CBF was reduced to <18 mL · 100
g-1 · min-1,
averaging 14±6 mL · 100 g-1 ·
min-1 in the motor area of the parietal cortex
and 16±7 mL · 100 g-1 ·
min-1 in the adjacent occipital cortex A18
(Figures 2 and 3). These values for CBF were
significantly lower than those on the contralateral side. In areas
adjacent to the impact site, occipital cortex area A18a and the
hippocampus, CBF was significantly lower on the impacted side than on
the contralateral side, and CBF was reduced in the TBI+BCO group
compared with the TBI group (Table 2). However, CBF remained
>18 mL · 100 g-1 ·
min-1 at these sites.
|
|
PbtO2 Studies
The results of the PbtO2
studies are illustrated in Figures 4 and 5 for the TBI and TBI+BCO groups,
respectively. In each figure, the arrow labeled CBF illustrates the
timing of the autoradiographic CBF studies discussed
earlier. PbtO2 averaged
24.6±8.3 mm Hg before the impact injury and changed
significantly during the TBI experiment (side effect
P=0.011, time effect P<0.001, sidextime
interaction P=0.015) and during the TBI+BCO experiment (side
effect P=0.002, time effect P<0.001, sidextime
interaction, P<0.001).
|
|
The animals that received only the 3-m/s impact injury (TBI group) had a significant reduction in PbtO2 to <10 mm Hg immediately after the impact injury. The PbtO2 gradually increased but was still less than control values and less than that of the contralateral side at 2 hours after the impact injury. At the time of the CBF measurement discussed earlier (rCBF in the impact site 53±24 mL · 100 g-1 · min-1), the average PbtO2 at the impact site was 9.3±2.9 mm Hg.
In the animals that received the combined impact injury followed by
carotid occlusion (TBI+BCO group), the
PbtO2 also decreased to <10
mm Hg at the impact site after the impact injury. During the carotid
occlusion, the PbtO2 at the impact
site decreased to 1.3±1.6 mm Hg at the time of the CBF
measurement discussed earlier (CBF 14±3 mL · 100
g-1 · min-1)
compared with 5.5±2.5 mm Hg on the contralateral side. At this
time, 3 of 6 animals had a PbtO2 of
0 mm Hg and 5 of 6 animals had a
PbtO2 of <3 mm Hg at the
impact site. In contrast, PbtO2 was
3 mm Hg on the contralateral side in all animals
(P=0.008, Fisher’s exact test).
There were no changes in the measured physiological parameters during the experiment that account for the differences in PbtO2 observed in the 2 treatment groups. Arterial blood gases, rectal temperature, and mean arterial blood pressure did not significantly vary throughout the study or between groups. The calibration check of the PO2 catheters at the end of the study showed minimal drift of the PO2 readings during the experiment. In zero oxygen solution, the average PO2 was 0.1±0.2 mm Hg, and in room air, the average PO2 was 155.7±3.6 mm Hg.
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferencesIntroduction |
|---|
TBI results in a reduction in CBF in many experimental models. However, it has never been clear whether this reduction in CBF causes any additional damage to the brain. CBF in the present study either was not sufficiently reduced to be considered ischemic or was markedly reduced only at the impact site, where tissue was badly damaged. The reduction in CBF in this circumstance may simply be a reflection of the severity of the primary damage to the cortical tissue. Finally, ischemic thresholds for CBF may be different after TBI, because cerebral metabolic requirements may be altered by the tissue response to the trauma.
In the fluid percussion injury, global CBF is reduced to approximately 50% of normal levels by 30 minutes to 1 hour after injury.27 28 29 By 2 hours after lateral fluid percussion injury, CBF returned to near normal values in all areas except at the actual impact site.30
In the controlled cortical impact injury model, CBF is reduced primarily at the impact site in mild injury24 31 With more severe injury, the reduction in CBF is global, although the greatest decrease in CBF is always at the impact site31 32 CBF does decrease to <18 mL · 100 g-1 · min-1 at the impact site in this model, and there is a tendency for the volume of tissue with CBF values of <18 to 20 mL · 100 g-1 · min-1 to increase from 30 minutes to 4 hours after injury.31
CBF must be considered within the context of cerebral metabolic requirements, which are known to be altered after TBI. Studies that have measured the glucose metabolic rate after experimental TBI suggest that the metabolic rate is initially increased as large amounts of energy are expended in the regain of ionic concentration gradients.33 Later, cerebral metabolic rate is decreased.33 34 Similar findings have been observed in human brain injury.35 The initial increased metabolic requirements tend to increase the CBF threshold, which would result in energy depletion, and the later decreased metabolic rate tends to decrease the CBF threshold, which would result in energy depletion. Therefore, the ischemia threshold of 18 mL · 100 g-1 · min-1, which was established in normal brain, may not apply after trauma. In such circumstances, the measurement of cerebral oxygenation can provide additional information about the relative adequacy of the CBF.
The present study contributes information to 2 issues regarding the CBF response to TBI in the cortical impact injury model. First, the reduction in CBF at the impact site to an average value of 53±24 mL · 100 g-1 · min-1 is not simply a physiological response to reduced cerebral metabolic requirements caused by the 3-m/s impact injury. The PbtO2, which averaged 9.3±2.9 mm Hg at the time of the low CBF measurement at the impact site, was significantly lower than the normal value of 24.6±8.3 mm Hg measured before the impact injury and was significantly lower than that on the contralateral side throughout most of the postimpact period of monitoring. The surface area of the PO2 probe used for these measurements is sufficiently large for the resulting measure to be an average tissue PO2 in the region surrounding the probe. The local variability in tissue PO2 observed with microelectrode measurements is not found with this probe. Normal PbtO2 measured with these probes is typically 20 to 40 mm Hg, and reductions to 8 to 10 mm Hg are generally thought to be critical reductions in cerebral oxgyenation.36 37 38
Because previous studies have documented that the injury level used in the present study does not result in histological changes,11 it may be assumed that the observed reduction in CBF and oxygenation can be tolerated at least transiently without causing ischemic damage. However, if the reduction in CBF were an appropriate and physiological response to reduced cerebral metabolic requirements, then tissue oxygenation should not have decreased. Although the level of PbtO2 observed in the impacted brain is not sufficiently low to result in permanent damage by itself, it does indicate a degree of hypoperfusion and perhaps also a vulnerability to additional ischemic insults.
Second, when the injured brain, which already has a reduced baseline CBF value, is confronted with a secondary ischemic insult, the cerebral vasculature is not able to maintain an adequate level of perfusion at the impact site. CBF in the impacted brain tissue fell during the carotid occlusion period to levels that would normally be considered ischemic (<18 mL · 100 g-1 · min-1). PbtO2 also fell to very low values (<3 mm Hg) during the carotid occlusion period, indicating that the reduced CBF was inadequate to prevent oxygen depletion. Finally, because previous studies have found that 40 minutes of BCO after a 3-m/s, 2.5-mm deformation impact injury causes a large contusion (median volume 15.5 mm3) at the impact site and a decrease in the neuron density of both CA1 and CA3 regions of the hippocampus,11 the present CBF and PbtO2 findings suggest that ischemia may be associated with the tissue necrosis that develops at the impact site.
There were no systemic factors that might have contributed to the CBF findings. Past studies in which the cardiovascular response to impact injury of varying degrees of severity was studied suggested that this very mild impact injury causes only a small decrease in blood pressure and no increase in intracranial pressure.31 This was consistent with the blood pressure and blood gas findings of the present study, suggesting that the CBF findings were due to local factors.
Isoflurane has important effects on CBF and metabolism, and it should be considered whether the results were influenced by the anesthetic agent used in the present study. Isoflurane typically increases CBF in a dose-response manner.39 40 PbtO2 increases with CBF during isoflurane anesthesia.41 Therefore, it is unlikely that the reductions in CBF that occur with trauma or during carotid occlusion can be explained by anesthetic effects. Isoflurane may contribute to the relatively high CBF values measured in the noninjured areas of the brain in the TBI group, but the normal PbtO2 values in this group suggest that the measured CBF values are probably appropriate for metabolic requirements.
In summary, the results of the present study suggest a mechanism for increased susceptibility to secondary injury caused by trauma. Cerebrovascular dysfunction at the site of trauma puts the injured area at risk for secondary injury. Although cellular processes, which are independent of flow, may be involved, its relative contribution in this model is uncertain.
|
Acknowledgments |
|---|
This work was funded by NIH grant PO1-NS27616.
Received July 12, 1999; revision received December 21, 1999; accepted December 21, 1999.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferencesIntroduction |
|---|
1. Chesnut RM, Marshall LF, Klauber MR, Blunt BA, Baldwin N, Eisenberg HM, Jane JA, Marmarou A, Foulkes MA. The role of secondary brain injury in determining outcome from severe head injury. J Trauma. 1993;34:216–222.[Medline] [Order article via Infotrieve]
2. Chesnut RM. Secondary brain insults after head injury: clinical perspectives. New Horiz. 1995;3:366–375.[Medline] [Order article via Infotrieve]
3. Kohi YM, Mendelow AD, Teasdale GM, Allardice GM. Extracranial insults and outcome in patients with acute head injury: relationship to the Glasgow Coma Scale. Injury. 1984;16:25–29.[Medline] [Order article via Infotrieve]
4.
Miller JD, Sweet RC, Narayan RK, Becker DP. Early
insults to the injured brain. JAMA. 1978;240:439–442.
5. Miller JD, Becker DP. Secondary insults to the injured brain. J R Coll Surg Edinb. 1982;27:292–298.[Medline] [Order article via Infotrieve]
6. Wald S, Fenwick J, Shackford S. The effect of secondary insults on mortality and longterm disability of severe brain injury in a rural region without a trauma system. J Trauma. 1991;31:1041.
7. Pietropaoli JA, Rogers FB, Shackford SR, Wald SL, Schmoker JD, Zhuang J. The deleterious effects of intraoperative hypotension on outcome in patients with severe head injuries. J Trauma. 1992;33:403–407.[Medline] [Order article via Infotrieve]
8. Jones PA, Piper IR, Corrie J, Anderson SI, Housley AM, Midgley S, Tocher JL, Slattery J, Dearden NM, Andrews PJD, Miller JD. Microcomputer based detection of secondary insults and 12 month outcome after head injury. J Neurotrauma. 1993;10(suppl 1):S102. Abstract.
9. Piek J, Chesnut RM, Marshall LF, van Berkum Clark M, Klauber MR, Blunt BA, Eisenberg HM, Jane JA, Marmarou A, Foulkes MA. Extracranial complications of severe head injury. J Neurosurg. 1992;77:901–907.[Medline] [Order article via Infotrieve]
10.
Gopinath SP, Robertson CS, Contant CF, Hayes C, Feldman
Z, Narayan RK, Grossman RG. Jugular venous desaturation and outcome
after head injury. J Neurol. Neurosurg Psychiatr. 1994;57:717–723.
11. Cherian L, Robertson CS, Goodman JC. Secondary insults increase injury after controlled cortical impact in rats. J Neurotrauma. 1996;13:371–383.[Medline] [Order article via Infotrieve]
12. Jenkins LW, Moszynski D, Lyeth BG, Lewelt W, DeWitt DS, Allen A, Dixon CD, Povlishock JT, Majewski TJ, Clifton GL, Young HF, Becker DP, Hayes RL. Increased vulnerability of the mildly traumatized rat brain to cerebral ischemia: the use of controlled secondary ischemia as a research tool to identify common or different mechanisms contributing to mechanical and ischemic brain injury. Brain Res. 1989;477:211–224.[Medline] [Order article via Infotrieve]
13. Ishige N, Pitts LH, Berry I, Nishimura MC, James TL. The effects of hypovolemic hypotension on high-energy phosphate metabolism of traumatized brain in rats. J Neurosurg. 1988;68:129–136.[Medline] [Order article via Infotrieve]
14. Ishige N, Pitts LH, Berry I, Carlson SG, Nishimura MC, Moseley ME, Weinstein PR. The effect of hypoxia on traumatic head injury in rats: alterations in neurologic function, brain edema, and cerebral blood flow. J Cereb Blood Flow Metab. 1987;7:759–767.[Medline] [Order article via Infotrieve]
15. Tsuji O, Marmarou A, Bullock RM. Microdialysis detection of electrolytes and amino acids changes following head impact acceleration injury coupled with secondary insult. In: Nagai H, Kamiya K, Ishii S, eds. Intracranial Pressure IX. Tokyo, Japan: Springer-Verlag; 1994:268–270.
16. DeWitt DS, Jenkins LW, Prough DS. Enhanced vulnerability to secondary ischemic insults after experimental traumatic brain injury. New Horiz. 1995;3:376–383.[Medline] [Order article via Infotrieve]
17. Lewelt W, Jenkins LW, Miller JD. Effects of experimental fluid-percussion injury of the brain on cerebrovascular reactivity to hypoxia and to hypercapnia. J Neurosurg. 1982;56:332–338.[Medline] [Order article via Infotrieve]
18. Lewelt W, Jenkins LW, Miller JD. Autoregulation of cerebral blood flow after experimental fluid percussion injury of the brain. J Neurosurg. 1980;53:500–506.[Medline] [Order article via Infotrieve]
19. Proctor HJ, Palladino GW, Fillipo D. Failure of autoregulation after closed head injury: an experimental model. J Trauma. 1988;28:347–352.[Medline] [Order article via Infotrieve]
20. Enevoldsen EM, Jensen JT. Autoregulation and CO2 responses of cerebral blood flow in patients with severe head injury. J Neurosurg. 1978;48:689–703.[Medline] [Order article via Infotrieve]
21. Muizelaar JP, Ward JD, Marmarou A, Newlon PG. Cerebral blood flow and metabolism in severely head-injured children: part 2: autoregulation. J Neurosurg. 1989;71:72–76.[Medline] [Order article via Infotrieve]
22. Newell DW, Weber JP, Watson R, Aaslid R, Winn HR. Effect of transient moderate hyperventilation on dynamic cerebral autoregulation after severe head injury. Neurosurgery. 1996;39:35–44.[Medline] [Order article via Infotrieve]
23. Kohmura E, Yamada K, Hayakawa T, Kinoshita A, Matumoto K, Mogami H. Hippocampal neurons become more vulnerable to glutamate after subcritical hypoxia: an in vitro study. J Cereb Blood Flow Metab. 1990;10:877–884.[Medline] [Order article via Infotrieve]
24. Bryan RM Jr, Cherian L, Robertson C. Regional cerebral blood flow after controlled cortical impact injury in rats. Anesth Analg. 1995;80:687–695.[Abstract]
25.
Bryan RM Jr, Myers CL, Page RB. Regional
neurohypophysial and hypothalamic blood flow in rats during
hypercapnia. Am J Physiol. 1988;255:R295–R305.
26. Palkovits M, Brownstein JM. Maps and Guide to Microdissection of the Rat Brain. New York, NY: Elsevier; 1988.
27. Yuan XQ, Prough DS, Smith TL, DeWitt DS. The effects of traumatic brain injury on regional cerebral blood flow in rats. J Neurotrauma. 1988;5:289–301.[Medline] [Order article via Infotrieve]
28. Muir JK, Tynan M, Caldwell R, Ellis EF. Superoxide dismutase improves posttraumatic cortical blood flow in rats. J Neurotrauma. 1995;12:179–188.[Medline] [Order article via Infotrieve]
29. Dietrich WD, Alonso O, Busto R, Prado R, Dewanjee S, Dewanjee MK, Ginsberg MD. Widespread hemodynamic depression and focal platelet accumulation after fluid percussion brain injury: a double-label autoradiographic study in rats. J Cereb Blood Flow Metab. 1996;16:481–489.[Medline] [Order article via Infotrieve]
30. Yamakami I, McIntosh TK. Effects of traumatic brain injury on regional cerebral blood flow in rats as measured with radiolabeled microspheres. J Cereb Blood Flow Metab. 1989;9:117–124.[Medline] [Order article via Infotrieve]
31. Cherian L, Robertson CS, Contant CF Jr, Bryan RM Jr. Lateral cortical impact injury in rats: cerebrovascular effects of varying depth of cortical deformation and impact velocity. J Neurotrauma. 1994;11:573–585.[Medline] [Order article via Infotrieve]
32. Kochanek PM, Marion DW, Zhang W, Schiding JK, White M, Palmer AM, Clark RS, O’Malley ME, Styren SD, Ho C. Severe controlled cortical impact in rats: assessment of cerebral edema, blood flow and contusion volume. J Neurotrauma. 1995;12:1015–1025.[Medline] [Order article via Infotrieve]
33. Yoshino A, Hovda DA, Kawamata T, Katayama Y, Becker DP. Dynamic changes in local cerebral glucose utilization following cerebral concussion in rats: evidence of a hyper- and subsequent hypometabolic state. Brain Res. 1991;561:106–119.[Medline] [Order article via Infotrieve]
34. Hovda DA, Yoshino A, Kawamata T, Katayama Y, Becker DP. Diffuse prolonged depression of cerebral oxidative metabolism following concussive brain injury in the rat: a cytochrome oxidase histochemistry. Brain Res. 1991;567:1–10.[Medline] [Order article via Infotrieve]
35. Bergsneider M, Hovda DA, Shalmon E, Kelly DF, Vespa PM, Martin NA, Phelps ME, McArthur DL, Caron MJ, Kraus JF, Becker DP. Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study. J Neurosurg. 1997;86:241–251.[Medline] [Order article via Infotrieve]
36. Meixensberger J, Dings J, Kuhnigk H, Roosen K. Studies of tissue PO2 in normal and pathological human brain cortex. Acta Neurochir Suppl (Wien). 1993;59:58–63.[Medline] [Order article via Infotrieve]
37. Valadka A, Gopinath SP, Contant CF, Uzura M, Robertson CS. Critical values for brain tissue PO2 to outcome after severe head injury. Crit Care Med. 1998;26:1576–1581.[Medline] [Order article via Infotrieve]
38. Kiening KL, Unterberg AW, Bardt TF, Schneider GH, Lanksch WR. Monitoring of cerebral oxygenation in patients with severe head injuries: brain tissue PO2 versus jugular vein oxygen saturation. J. Neurosurg. 1996;85:751–757.[Medline] [Order article via Infotrieve]
39.
Hoffman WE, Edelman G, Kochs E, Werner C, Segil L,
Albrecht RF. Cerebral autoregulation in awake versus
isoflurane-anesthetized rats. Anesth Analg. 1991;73:753–757.
40.
Lee JG, Hudetz AG, Smith JJ, Hillard CJ, Bosnjak ZJ,
Kampine JP. The effects of halothane and isoflurane on cerebrocortical
microcirculation and autoregulation as assessed by laser-Doppler
flowmetry. Anesth Analg. 1994;79:58–65.
41.
Murr R, Schurer L, Berger S, Enzenbach R, Peter K,
Baethmann A. Effects of isoflurane, fentanyl, or thiopental
anesthesia on regional cerebral blood flow and brain
surface PO2 in the presence of a focal lesion in
rabbits. Anesth Analg. 1993;77:898–907.
Editorial Comment
Department of Neurological Surgery, University of California, Davis, Sacramento, California
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferencesIntroduction |
|---|
The article by Giri et al represents the thoughtful execution and presentation of these animal data concerning secondary brain injury. This study provides compelling and interesting evidence of a dysfunction of cerebral blood flow regulation at the site of a mild brain injury that renders that area of the brain unable to accommodate a global drop in blood flow. Their findings are of interest to those of us who have puzzled over the grave consequences of systemic hypotension after head injury or stroke, and they provide data that are important pieces of that puzzle. Specifically, the presence of a mild cortical impact injury results in a local impairment of blood flow and oxygen tension. The next step is to elucidate the pathophysiology of this phenomenon and attempt to prevent its occurrence.
Also, having worked with the Licox probe in animals, I know the difficulties involved in using bilateral probes in a rat brain. One should be skeptical in interpreting these types of data, because, in my hands at least, it is very easy to corrupt the data due to technical factors alone. This results in wide variation in the PO2 data from rat to rat and even from hemisphere to hemisphere. However, the data presented here are very clean. Clearly, the authors have a talent for it.
The take-away message for clinicians is that it is the local environment in the brain due to the injury that makes the brain susceptible to secondary insults and not the secondary insult per se. For me personally, it provides further hope that there will be intervention, pharmacological or otherwise, that may ameliorate the consequences of traumatic brain injury.
Received July 12, 1999; revision received December 21, 1999; accepted December 21, 1999.
This article has been cited by other articles:
 |
|
 |
|
  M. K. Wilkerson, L. A. Lesniewski, E. M. Golding, R. M. Bryan Jr., A. Amin, E. Wilson, and M. D. Delp Simulated microgravity enhances cerebral artery vasoconstriction and vascular resistance through endothelial nitric oxide mechanism Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1652 - H1661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Cherian, G. Chacko, C. Goodman, and C. S. Robertson Neuroprotective Effects of L-Arginine Administration after Cortical Impact Injury in Rats: Dose Response and Time Window J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 617 - 623. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||