Stereological assessment of vulnerability of immunocytochemically identified striatal and hippocampal neurons after global cerebral ischemia in rats.
Detailed quantitative analysis of the vulnerability of different hippocampal and striatal neurons to global forebrain ischemia has not previously been performed. Here we have studied the survival of immunocytochemically identified neurons using an unbiased stereological method in rats subjected to global forebrain ischemia for 30 min and sacrificed 48 h, 1 week or 4 weeks thereafter. Within the hippocampal formation, there was extensive, progressive loss of CA1 pyramidal neurons and dentate hilar neuropeptide Y (NPY)-positive interneurons. In contrast, no reduction of the number of CA3 and CA4 pyramidal neurons or hilar parvalbumin-positive interneurons was detected. In the dorsolateral striatum, the insult caused a major loss of projection neurons immunoreactive to dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein with a molecular weight of 32 kilodalton (DARPP-32). The number of parvalbumin-positive striatal interneurons was significantly reduced, while NPY-positive interneurons were resistant. All striatal cholinergic interneurons survived the ischemic insult. At 48 h following the ischemia, the cholinergic interneurons within the lesioned striatum transiently expressed the p75 neurotrophin receptor (p75(NTR)), as shown by double-label immunocytochemistry. Furthermore, there was a significant increase in the number of choline acetyltransferase (ChAT)- and TrkA-immunoreactive interneurons at 4 weeks after the insult. Injections with the cell mitotic division marker BrdU provided no evidence that the elevated cholinergic cell number was due to neurogenesis. Probably, the higher number of ChAT- and TrkA-positive interneurons reflected increased intracellular levels of the corresponding proteins leading to more cells detectable with immunocytochemistry. This study gives the first quantitative description of the vulnerability of defined hippocampal and striatal neurons after global forebrain ischemia. The ischemia-induced increases of p75(NTR), TrkA and ChAT in cholinergic striatal interneurons at various time points after the insult suggest that neurotrophin signaling might be important for the survival and function of these cells in the post-ischemic phase.
Larsson
E
E
Section of Restorative Neurology, Wallenberg Neuroscience Center, BMC A11, University Hospital, SE-221 84, Lund, Sweden. elin.larsson@neurol.lu.se
Lindvall
O
O
Kokaia
Z
Z
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D005452:Fluoresceins; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism / Q000473:pathology; D008297:Male; D017072:Neostriatum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009478:Neuropeptide Y / Q000378:metabolism; D009930:Organic Chemicals; D010320:Parvalbumins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism
D000954:Antigens, Surface; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D005452:Fluoresceins; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D009930:Organic Chemicals; D010320:Parvalbumins; D010750:Phosphoproteins; D020800:Receptor, Nerve Growth Factor; C435731:fluoro jade; D002795:Choline O-Acetyltransferase; D020917:Receptor, trkA