Consequential apoptosis in the cerebellum following injury to the developing rat forebrain.
In focal brain lesions, alterations in blood flow and cerebral metabolism can be detected in brain areas remote from the primary injury. The cellular consequences of this phenomenon, originally termed diaschisis, are not fully understood. Here, we report that in two distinct models of forebrain injury, neuronal death in the cerebellum, a site distant to the primary injury, results as consequence of neuronal loss in the forebrain. Fourteen-day-old rats were subjected to unilateral forebrain injury, achieved by either hypoxia-ischemia (right carotid artery ligation and hypoxia) or direct needle injury to brain tissue. At defined times after injury, the presence of apoptosis was investigated by cell morphology, in situ end labeling, electron microscopy and poly-ADP-ribose polymerase (PARP) cleavage. Injury to the rat forebrain following hypoxia-ischemia increased apoptosis in the internal granular and Purkinje cell layers of the cerebellum, a site distant to that of the primary injury. The number of apoptotic cells in the cerebellum was significantly related to cell death in the hippocampus. Similarly, direct needle injury to the forebrain resulted in extensive apoptotic cell death in the cerebellum. These results emphasize the intimate relationship between defined neuronal populations in relatively distant brain areas and suggest a cellular basis for diaschisis.
Taylor
Deanna L
DL
Division of Clinical Sciences, Imperial College London, UK.
Joashi
Umesh C
UC
Sarraf
Catherine
C
Edwards
A David
AD
Mehmet
Huseyin
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002531:Cerebellum / Q000254:growth & development* / Q000473:pathology*; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology; D017403:In Situ Hybridization; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000648:ultrastructure; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016548:Prosencephalon / Q000254:growth & development* / Q000293:injuries*; D051381:Rats; D017208:Rats, Wistar
D011065:Poly(ADP-ribose) Polymerases