Enhanced neurogenesis after transient global ischemia in the dentate gyrus of the rat

The dentate gyrus is one of the few areas of the mammalian brain where new neurons are continuously produced in adulthood. Certain insults such as epileptic seizures and ischemia are known to enhance the rate of neuronal production. We analyzed this phenomenon using the temporary occlusion of the tw...

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Published in:Experimental brain research 2001-02, Vol.136 (3), p.313-320
Main Authors: KEE, N. J, PRESTON, E, WOJTOWICZ, J. M
Format: Article
Language:English
Subjects:
Animals
Antimetabolites
Axon guidance
Axonogenesis
Biological and medical sciences
Bromodeoxyuridine
Calbindin
Calbindins
Calcium-binding protein
Carotid artery
Cell differentiation
Cell Differentiation - physiology
Cell Division - physiology
Cell Survival - physiology
Cerebral blood flow
Cytoplasm - chemistry
Dentate gyrus
Dentate Gyrus - blood supply
Dentate Gyrus - cytology
Epilepsy
Granule cells
Hypotension
Ischemia
Ischemic Attack, Transient - pathology
Maturation
Medical sciences
Neurogenesis
Neurology
Neurons - chemistry
Neurons - cytology
Rats
Rats, Sprague-Dawley
S100 Calcium Binding Protein G - analysis
Seizures
Stroke - pathology
Vascular diseases and vascular malformations of the nervous system
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PRESTON, E
WOJTOWICZ, J. M
description The dentate gyrus is one of the few areas of the mammalian brain where new neurons are continuously produced in adulthood. Certain insults such as epileptic seizures and ischemia are known to enhance the rate of neuronal production. We analyzed this phenomenon using the temporary occlusion of the two carotid arteries combined with arterial hypotension as a method to induce ischemia in rats. We measured the rate of cell production and their state of differentiation with a mitotic indicator, bromodeoxyuridine (BrdU), in combination with the immunohistochemical detection of neuronal markers. One week after the ischemic episode, the cell production in dentate gyrus was increased two- to threefold more than the basal level seen in control animals. Two weeks after ischemia, over 60% of these cells became young neurons as determined by colabeling with BrdU and a cytoplasmic protein (CRMP-4) involved in axonal guidance during development. Five weeks after the ischemia, over 60% of new neurons expressed calbindin, a calcium-binding protein normally expressed in mature granule neurons. In addition to more cells being generated, a greater proportion of all new cells remained in the differentiated but not fully mature state during the 2- to 5-week period after ischemia. The maturation rate of neurons as determined by the calbindin labeling and by the rate of migration from a proliferative zone into the granule cell layer was not changed when examined 5 weeks after ischemia. The results support the hypothesis that survival of dentate gyrus after ischemia is linked with enhanced neurogenesis. Additional physiological stimulation after ischemia may be exploited to stimulate maturation of new neurons and to offer new therapeutic strategies for promoting recovery of neuronal circuitry in the injured brain.
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In addition to more cells being generated, a greater proportion of all new cells remained in the differentiated but not fully mature state during the 2- to 5-week period after ischemia. The maturation rate of neurons as determined by the calbindin labeling and by the rate of migration from a proliferative zone into the granule cell layer was not changed when examined 5 weeks after ischemia. The results support the hypothesis that survival of dentate gyrus after ischemia is linked with enhanced neurogenesis. Additional physiological stimulation after ischemia may be exploited to stimulate maturation of new neurons and to offer new therapeutic strategies for promoting recovery of neuronal circuitry in the injured brain.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>11243473</pmid><doi>10.1007/s002210000591</doi><tpages>8</tpages></addata></record>
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subjects Animals
Antimetabolites
Axon guidance
Axonogenesis
Biological and medical sciences
Bromodeoxyuridine
Calbindin
Calbindins
Calcium-binding protein
Carotid artery
Cell differentiation
Cell Differentiation - physiology
Cell Division - physiology
Cell Survival - physiology
Cerebral blood flow
Cytoplasm - chemistry
Dentate gyrus
Dentate Gyrus - blood supply
Dentate Gyrus - cytology
Epilepsy
Granule cells
Hypotension
Ischemia
Ischemic Attack, Transient - pathology
Maturation
Medical sciences
Neurogenesis
Neurology
Neurons - chemistry
Neurons - cytology
Rats
Rats, Sprague-Dawley
S100 Calcium Binding Protein G - analysis
Seizures
Stroke - pathology
Vascular diseases and vascular malformations of the nervous system
title Enhanced neurogenesis after transient global ischemia in the dentate gyrus of the rat
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