Lesions of excitatory pathways reduce hippocampal cell death after transient forebrain ischemia in the gerbil.
Transient forebrain ischemia produces a spatially and temporally selective pattern of neuronal degeneration in the hippocampal formation of the Mongolian gerbil. Ischemic neuronal death has been suggested to depend on the activation of excitatory hippocampal pathways that project to the vulnerable neurons. This idea was tested by examining the effect of a unilateral entorhinal cortical lesion or a unilateral knife cut lesion of intrahippocampal pathways on the neuropathology produced by 5 min of complete forebrain ischemia. A prior lesion of either the ipsilateral entorhinal cortex or the mossy fiber and Schaffer collateral-commissural pathways partially prevented the destruction of CA1b pyramidal cells in most animals. It did not, however, reduce the extent of ischemic neuronal death in any other hippocampal subfield. Within area CA1b, an entorhinal lesion protected an average of 23% of the pyramidal cells and a transection of both mossy and Schaffer collateral-commissural fibers protected an average of 36.5%. CA1b pyramidal cells saved from ischemia-induced degeneration appeared clearly abnormal when stained with cresyl violet or by silver impregnation. It is suggested that lesions of excitatory pathways attenuate ischemic damage to area CA1b by directly or indirectly reducing the level of synaptic excitation onto the vulnerable neurons. However, only a relatively small percentage of hippocampal neurons can be protected by these lesions in the gerbil ischemia model and there is reason to believe that the neurons protected in this manner may not be electrophysiologically competent. Synaptic excitation therefore appears to play an important, but not an essential, role in this model of ischemic brain damage.
Department of Pathology, Duke University Medical Center, Durham, NC 27710.
T M
TM
Kaplan
T M
TM
Lasner
J V
JV
Nadler
B J
BJ
Crain
D000344:Afferent Pathways / Q000473:pathology*; D000818:Animals; D002470:Cell Survival; D005849:Gerbillinae; D006624:Hippocampus / Q000473:pathology*; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male