Interneurons in rat hippocampus after cerebral ischemia. Morphometric, functional, and therapeutic investigations

Acta Neurol Scand Suppl. 1993;150:1-32.


This review describes the neuropathology and pathophysiology of interneurons in dorsal hippocampus of the adult rat subjected to transient global cerebral ischemia. The object is to verify if the interneurons die or survive after an ischemic insult, and study if ischemia changes GABA inhibition in the period preceding delayed CA1 pyramidal cell death. The findings are discussed from the point of the hypothesis that loss of GABA inhibition may result in excitatory hyperactivity (possibly epilepsy) and excitotoxic glutamate release. Thereby, early ischemic damage to interneurons may exacerbate the ischemic process resulting in the major and delayed CA1 cell death in hippocampus. Interneurons, located in dentate hilus, and a small number of interneurons located in the mossy fiber layer are selectively lost after ischemia. These interneurons contain somatostatin and neuropeptide Y, but the inhibitory or excitatory nature of them is unknown. However, counts of all hippocampal cells immunoreactive for glutamic acid decarboxylase showed that the GABA interneurons survive ischemia. It is therefore suggested that the vulnerable interneurons in hilus and the mossy fiber layer do not contain GABA. As the GABA interneurons, other hippocampal interneurons also survive ischemia. Among these, the CA1 and CA3 interneurons containing neuropeptide Y demonstrate permanently reduced immunoreactivity for neuropeptide Y, evident 1-2 days after ischemia. Another subpopulation transiently shows a decrease in immunoreactivity for parvalbumin approximately 4 days after ischemia. These results are in contrast to the finding that protein synthesis in hippocampal interneurons returns to preischemic levels 9 hours after ischemia. The integrity between excitation and inhibition in CA1 is unchanged in hippocampal slices taken from animals 1-2 days after ischemia. Furthermore, GABA can readily be released upon potassium stimulation in the period preceding CA1 pyramidal cell death. Binding to hippocampal benzodiazepine sites, however, declines prior to ischemic CA1 pyramidal cell death. It is demonstrated that administration of diazepam and GABA uptake inhibitors during this period offers postischemic neuron protection in CA1. There is no conclusive evidence of excitatory hyperactivity preceding ischemic CA1 pyramidal cell death. On the contrary, results from Chang et al. (1) suggest that ischemic loss of interneurons in the dentate hilus is associated with an increase in inhibition. However, it is suggested that GABA inhibition is insufficient to counterbalance the detrimental process during normal or even reduced postischemic excitation, since drugs believed to increase GABA inhibition reduce ischemic cell death. The early and permanent reduction in neuropeptide Y immunoreactivity may reflect a reduced capacity of these interneurons to release neuropeptide Y and thereby reduce presynaptic glutamate release.(ABSTRACT TRUNCATED AT 400 WORDS)

Publication types

  • Review

MeSH terms

  • Animals
  • Autoradiography
  • Brain Ischemia / pathology*
  • Brain Ischemia / physiopathology
  • Calcium-Binding Proteins / metabolism
  • Cell Death
  • Cholecystokinin / metabolism
  • Disease Models, Animal
  • Glutamate Decarboxylase / metabolism
  • Hippocampus / pathology*
  • Hippocampus / physiopathology
  • Interneurons / pathology*
  • Interneurons / physiology
  • Neuropeptide Y / metabolism
  • Pyramidal Cells / pathology
  • Pyramidal Cells / physiology
  • Rats
  • Receptors, GABA / physiology
  • Somatostatin / metabolism
  • gamma-Aminobutyric Acid / physiology


  • Calcium-Binding Proteins
  • Neuropeptide Y
  • Receptors, GABA
  • Somatostatin
  • gamma-Aminobutyric Acid
  • Cholecystokinin
  • Glutamate Decarboxylase