A histopathological study of premature and mature infants with pontosubicular neuron necrosis: neuronal cell death in perinatal brain damage.
Perinatal hypoxic-ischemic brain damage is a major cause of neuronal and behavior deficits, in which the onset of injury can be before, at or after birth, and the effects may be delayed. Pontosubicular neuron necrosis (PSN) is one of perinatal hypoxic-ischemic brain injury and its pathological peculiarity is neuronal apoptosis. In this study, we investigated whether apoptotic cascade of PSN used a caspase-pathway or not, and whether hypoglycemia activated apoptosis or not. Sections of the pons of PSN with and without hypoglycemia were stained using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and immunohistochemistry for glial fibrillary acidic protein (GFAP), Bcl-2, Bcl-x and activated caspase 3. Additionally, we performed immunoblot analysis of Bcl-2, Bcl-x and activated caspase 3. TUNEL-positive cell was closely associated with the presence of karyorrhexis. Under combination of karyorrhectic and TUNEL-positive cells, number of apoptotic cells in premature brains was significantly more than in mature brains. Hypoxic-ischemic brain injury was considered to easily lead to apoptosis in premature infants. Moreover, as this pathophysiology, caspase-pathway activation contributed to neuronal death from caspase-immunoexpression analyses. PSN with hypoglycemia showed large number of apoptotic cells and higher expression of activated caspase 3. The result may be more severe with the background of hypoglycemia and prematurity complicated by hypoxia and/or ischemia.
Takizawa
Yuji
Y
Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan.
Takashima
Sachio
S
Itoh
Masayuki
M
D000367:Age Factors; D000704:Analysis of Variance; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000502:physiology; D005865:Gestational Age; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007231:Infant, Newborn; D009336:Necrosis; D009474:Neurons / Q000473:pathology*; D047928:Premature Birth / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases