Effect of ibotenate on brain development: an excitotoxic mouse model of microgyria and posthypoxic-like lesions.

摘要: Ibotenate, a glutamatergic agonist, was injected in developing mouse neopallium. When at the time of completion supragranular neuronal migration (P0) ibotenate induces complete depopulation layers V-VI and an abnormal sulcation overlying layers. Injected after (P5-P10) produces severe loss II, III, IV, V, VI. After exposure to between P0 P5, surviving neurons have ability resume their migration, inducing neocortical pattern. Periventricular white matter lesions are observed injection P2-P10, with peak occurrence P5. Both gray damage prevented by DL-2-amino-7-phosphonoheptanoic acid, N-methyl-D-aspartate receptor antagonist, but not L (+)-2-amino-3-phosphonopropionic metabotropic glutamate antagonist. The microtubule-associated type 2 protein, dendritic marker, is absent all lesions, which reflects developmental impairment phase. These staged disclose sequence excitotoxin-affected events starting selective layered sensitivity postmigratory continuing astroglial maturation axonal growth. They faithfully mimic microgyrias, focal cortico-subcortical dysplasias, porencephalic cysts, human perinatal hypoxic/ischemic lesions. This model provides tools for investigating excitotoxic influences on neural development various stages identifying protective substances against excitotoxicity from hypoxic nonhypoxic origins.