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(Stroke. 2009;40:2173.)
© 2009 American Heart Association, Inc.

Original Contributions

Degeneration of Astrocytic Processes and Their Mitochondria in Cerebral Cortical Regions Peripheral to the Cortical Infarction

Heterogeneity of Their Disintegration Is Closely Associated With Disseminated Selective Neuronal Necrosis and Maturation of Injury

Umeo Ito, MD, PhD, FAHA; Yoji Hakamata, DVM, PhD; Emiko Kawakami, BS Kiyomitsu Oyanagi, MD, PhD

From the Department of Neuropathology (U.I., E.K., K.O.), Tokyo Metropolitan Institute for Neuroscience, Tokyo; and the Department of Basic Science (Y.H.), School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Japan.

Correspondence to Umeo Ito, MD, PhD, FAHA, Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu-shi, Tokyo 183-8526, Japan. E-mail umeo-ito{at}nn.iij4u.or.jp

Background and Purpose— Astrocytes support neuronal functions by regulating the extracellular ion-homeostasis and levels of neurotransmitters, and by providing fuel such as lactate to the neurons via their astrocytic processes (APs). Whether injured APs are associated with neuronal survival/death is still an unanswered question. We investigated APs in the neuropil, especially those around astrocytes and normal-appearing, degenerating, and dead neurons in cerebral cortical regions peripheral to the cortical infarction (RPI).

Methods— Stroke-positive gerbils were euthanized at various times after the ischemic insult. Ultrathin sections were obtained from the RPI sectioned coronally at the infundibular level. We counted the number of normal-appearing, degenerated, and dead neurons and astrocytes in paraffin sections, the number of cut-ends and mitochondria in APs in the neuropil on electron-microscopic photographs, and determined the percent-volume of APs by Weibel point-counting method. We compared the number of cut-ends and mitochondria and percent-volume of APs around astrocytes at 5 hours and 48 hours, and around normal-appearing, degenerated, and dead neurons at 12 hours.

Results— Although the number of astrocytes did not change (average of 12.3±0.20%) during 0 to 48 hours, that of the dead neurons increased from 9.71±1.34 to 44.39±1.40% during 5 to 48 hours postischemia. The number of normal-appearing APs and mitochondria in APs decreased respectively from 13.49±0.65 to 1.61±0.14/28.20 µm² and from 1.86±0.18 to 0.61±0.07/28.20 µm² in the neuropil during 0 to 48 hours. The number of normal-appearing APs around astrocytes decreased from 12.3±0.19 to 1.7±0.05/38.33 µm² with an increase in percent-volume of degenerated APs from 1.17±0.04 to 11.45±0.23%, from 5 to 48 hours postischemia. The number of normal-appearing APs decreased from 4.36±0.52 to1.56±0.17/38.33 µm² with an increase in percent-volume of degenerated APs, from 2.41±0.52 to 12.55±1.0%, from around the normal-appearing to dead neurons, at 12 hours.

Conclusions— In the RPI, heterogeneous degeneration of APs was closely associated with disseminated selective neuronal necrosis and the maturation phenomenon seen in ischemic neuronal injury.

Key Words: astrocytic process • mitochondria • ischemic penumbra • disseminated selective neuronal necrosis • maturation phenomenon • delayed neuronal death