This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hua, Y. Articles by Xi, G. Search for Related Content PubMed PubMed Citation Articles by Hua, Y. Articles by Xi, G. Related Collections Thrombin Acute Cerebral Hemorrhage Intracerebral Hemorrhage

(Stroke. 2002;33:2478.)
© 2002 American Heart Association, Inc.

Original Contributions

Behavioral Tests After Intracerebral Hemorrhage in the Rat

Ya Hua, MD; Timothy Schallert, PhD; Richard F. Keep, PhD; Jimin Wu, MD; Julian T. Hoff, MD Guohua Xi, MD

From the Departments of Neurosurgery (Y.H., T.S., R.F.K., J.W., J.T.H., G.X.) and Physiology (R.F.K.), University of Michigan, Ann Arbor, and Department of Psychology and Institute for Neuroscience, University of Texas at Austin (T.S.).

Reprint requests to Ya Hua, MD, R5550 Kresge I, University of Michigan, Ann Arbor, MI 48109-0532. E-mail yahua{at}umich.edu

Background and Purpose— In humans, intracerebral hemorrhage (ICH) causes marked perihematomal edema formation and neurological deficits. A rat ICH model, involving infusion of autologous blood into the caudate, has been used extensively to study mechanisms of edema formation, but an examination of behavioral outcome would improve its preclinical utility and provide a more rigorous assessment of the pathological cascade of events over time. The purpose of this study was to use a battery of sensorimotor function tests to examine the neurological effects of ICH in the rat and to examine which components of the hematoma are involved in generating those effects.

Methods— The behavioral tests used were forelimb placing, preference for forelimb use for weight shifts during vertical exploration of a cylindrical enclosure, and a corner turn test. Rats were tested from day 1 to day 28 after injection of autologous whole blood; injection of blood plus hirudin (thrombin inhibitor), packed red blood cells, thrombin, or saline; or needle placement only.

Results— The battery of tests indicated that there were marked neurological deficits by day 1 after ICH, with progressive recovery of function over 4 weeks. The forelimb placing score paralleled changes in edema. Injection of thrombin caused and injection of hirudin reduced the ICH-induced neurological deficits. Injection of packed red blood cells, which causes delayed edema formation, induced delayed neurological deficits

Conclusions— These tests allow continuous monitoring of neurological deficits after rat ICH and assessment of therapeutic interventions. The time course of the neurological deficit closely matched the time course of cerebral edema for both ICH and injection of blood components. There was marked recovery of function after ICH, which may be amenable to therapeutic manipulation.

Key Words: behavior, animal • brain edema • cerebral hemorrhage • erythrocytes • thrombin • rats

This article has been cited by other articles:

				M. Okauchi, Y. Hua, R. F. Keep, L. B. Morgenstern, and G. Xi Effects of Deferoxamine on Intracerebral Hemorrhage-Induced Brain Injury in Aged Rats Stroke, May 1, 2009; 40(5): 1858 - 1863. [Abstract] [Full Text] [PDF]

				T. Sugawara, V. Jadhav, R. Ayer, W. Chen, H. Suzuki, and J. H. Zhang Thrombin Inhibition by Argatroban Ameliorates Early Brain Injury and Improves Neurological Outcomes After Experimental Subarachnoid Hemorrhage in Rats Stroke, April 1, 2009; 40(4): 1530 - 1532. [Abstract] [Full Text] [PDF]

				Y. Hua, R. F. Keep, Y. Gu, and G. Xi Thrombin and Brain Recovery After Intracerebral Hemorrhage Stroke, March 1, 2009; 40(3_suppl_1): S88 - S89. [Abstract] [Full Text] [PDF]

				T. Kuroiwa, G. Xi, Y. Hua, T. N. Nagaraja, J. D. Fenstermacher, and R. F. Keep Development of a Rat Model of Photothrombotic Ischemia and Infarction Within the Caudoputamen Stroke, January 1, 2009; 40(1): 248 - 253. [Abstract] [Full Text] [PDF]

				S. Yang, S. Song, Y. Hua, T. Nakamura, R. F. Keep, and G. Xi Effects of Thrombin on Neurogenesis After Intracerebral Hemorrhage Stroke, July 1, 2008; 39(7): 2079 - 2084. [Abstract] [Full Text] [PDF]

				T. Nakamura, Y. Kuroda, S. Yamashita, X. Zhang, O. Miyamoto, T. Tamiya, S. Nagao, G. Xi, R. F. Keep, and T. Itano Edaravone Attenuates Brain Edema and Neurologic Deficits in a Rat Model of Acute Intracerebral Hemorrhage Stroke, February 1, 2008; 39(2): 463 - 469. [Abstract] [Full Text] [PDF]

				S. Song, Y. Hua, R. F. Keep, J. T. Hoff, and G. Xi A New Hippocampal Model for Examining Intracerebral Hemorrhage-Related Neuronal Death: Effects of Deferoxamine on Hemoglobin-Induced Neuronal Death Stroke, October 1, 2007; 38(10): 2861 - 2863. [Abstract] [Full Text] [PDF]

				K. L. Ward, I. Tkac, Y. Jing, B. Felt, J. Beard, J. Connor, T. Schallert, M. K. Georgieff, and R. Rao Gestational and Lactational Iron Deficiency Alters the Developing Striatal Metabolome and Associated Behaviors in Young Rats J. Nutr., April 1, 2007; 137(4): 1043 - 1049. [Abstract] [Full Text] [PDF]

				Y. Hua, R. F. Keep, J. T. Hoff, and G. Xi Brain Injury After Intracerebral Hemorrhage: The Role of Thrombin and Iron Stroke, February 1, 2007; 38(2): 759 - 762. [Abstract] [Full Text] [PDF]

				C. L. MacLellan, L. M. Davies, M. S. Fingas, and F. Colbourne The Influence of Hypothermia on Outcome After Intracerebral Hemorrhage in Rats Stroke, May 1, 2006; 37(5): 1266 - 1270. [Abstract] [Full Text] [PDF]

				J. Shao, G. Xi, Y. Hua, T. Schallert, and B. Felt Intracerebral Hemorrhage in the Iron-Deficient Rat Stroke, March 1, 2005; 36(3): 660 - 664. [Abstract] [Full Text] [PDF]

				NINDS ICH Workshop Participants Priorities for Clinical Research in Intracerebral Hemorrhage: Report From a National Institute of Neurological Disorders and Stroke Workshop Stroke, March 1, 2005; 36(3): e23 - e41. [Abstract] [Full Text] [PDF]

				T. Nakamura, G. Xi, J.-W. Park, Y. Hua, J. T. Hoff, and R. F. Keep Holo-Transferrin and Thrombin Can Interact to Cause Brain Damage Stroke, February 1, 2005; 36(2): 348 - 352. [Abstract] [Full Text] [PDF]

				Y. Gong, Y. Hua, R. F. Keep, J. T. Hoff, and G. Xi Intracerebral Hemorrhage: Effects of Aging on Brain Edema and Neurological Deficits Stroke, November 1, 2004; 35(11): 2571 - 2575. [Abstract] [Full Text] [PDF]

				L. Belayev, I. Saul, K. Curbelo, R. Busto, A. Belayev, Y. Zhang, P. Riyamongkol, W. Zhao, and M. D. Ginsberg Experimental Intracerebral Hemorrhage in the Mouse: Histological, Behavioral, and Hemodynamic Characterization of a Double-Injection Model Stroke, September 1, 2003; 34(9): 2221 - 2227. [Abstract] [Full Text] [PDF]