EFFECT OF IBOTENATE ON BRAIN-DEVELOPMENT - AN EXCITOTOXIC MOUSE MODELOF MICROGYRIA AND POSTHYPOXIC-LIKE LESIONS

Citation
S. Marret et al., EFFECT OF IBOTENATE ON BRAIN-DEVELOPMENT - AN EXCITOTOXIC MOUSE MODELOF MICROGYRIA AND POSTHYPOXIC-LIKE LESIONS, Journal of neuropathology and experimental neurology, 54(3), 1995, pp. 358-370
Citations number
61
Categorie Soggetti
Pathology,Neurosciences,"Clinical Neurology
ISSN journal
00223069
Volume
54
Issue
3
Year of publication
1995
Pages
358 - 370
Database
ISI
SICI code
0022-3069(1995)54:3<358:EOIOB->2.0.ZU;2-X
Abstract
Ibotenate, a glutamatergic agonist, was injected in developing mouse n eopallium. When injected at the time of completion of supragranular ne uronal migration (P0) ibotenate induces complete neuronal depopulation of layers V-VI and an abnormal sulcation of the overlying supragranul ar layers. Injected after completion of migration (P5-P10) ibotenate p roduces severe neuronal loss in layers II, III, IV, V, and VI. After e xposure to ibotenate between P0 and P5, surviving neurons have the abi lity to resume their migration, inducing an abnormal neocortical patte rn. Periventricular white matter lesions are observed after ibotenate injection at P2-P10, with a peak of occurrence at P5. Both gray and wh ite matter damage are prevented by DL-2-amino-7-phosphonoheptanoic aci d, an N-methyl-D-aspartate receptor antagonist, but not by L (+)-2-ami no-3-phosphonopropionic acid, a metabotropic glutamate receptor antago nist. The microtubule-associated type 2 protein, a dendritic marker, i s absent in all ibotenate lesions, which reflects the developmental im pairment of the dendritic phase. These staged lesions of the gray and white matter disclose a developmental sequence of excitotoxin-affected events starting with the selective and layered sensitivity of postmig ratory neocortical neurons and continuing in the white matter with the astroglial maturation and the axonal growth. They faithfully mimic mi crogyrias, focal cortico-subcortical dysplasias, porencephalic cysts, and white matter damage observed in human perinatal hypoxic/ischemic l esions. This mouse model provides tools for investigating excitotoxic influences on neural development at the various stages and for identif ying protective substances against excitotoxicity from hypoxic and fro m nonhypoxic origins.