Apoptosis and microglial activation in influenza encephalopathy.
During influenza epidemics in Japan, the number of children with acute encephalopathies and encephalitis has recently increased. Although the pathophysiologies remain unclear, there is usually brain edema with evidence of damage to the blood-brain-barrier (BBB). We investigated the glial reaction and apoptosis in brains of eight such cases comprising two of acute necrotizing encephalopathy and six of influenza encephalopathy, and compared the results with those in five control brains. Apoptosis, evidenced by chromatin condensation and fragmentation in hematoxylin sections, in situ end labeling of fragmented DNA (TUNEL) and DNA laddering, was observed in neurons and glial cells in four brains with influenza encephalopathy. In the TUNEL-positive brains, the increase in microglia was greater than in the TUNEL-negative brains. Immunoreactivity for active-caspase 3, demonstrated by immunohistochemistry, and the overexpression of a caspase-cleaved fragment of poly(ADP-ribose) polymerase, demonstrated by Western blotting, indicated that activation of caspase 3 is involved in the apoptotic pathway in the brains of influenza encephalopathy cases. Apoptosis or specific pathological processes that cause apoptosis may give rise to aggravated encephalopathy.
Nakai
Yoshiko
Y
Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, NCNP, Tokyo, Japan. ysuzuki@med.nagoya-u.ac.jp
Itoh
Masayuki
M
Mizuguchi
Masashi
M
Ozawa
Hiroshi
H
Okazaki
Etsuo
E
Kobayashi
Yasutsugu
Y
Takahashi
Mitsuo
M
Ohtani
Kyoichi
K
Ogawa
Akira
A
Narita
Michihiko
M
Togashi
Takehiro
T
Takashima
Sachio
S
D000293:Adolescent; D017209:Apoptosis; D015153:Blotting, Western; D001927:Brain Diseases / Q000209:etiology* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D020805:Central Nervous System Viral Diseases / Q000150:complications* / Q000473:pathology; D002675:Child, Preschool; D004660:Encephalitis / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007223:Infant; D008297:Male; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009975:Orthomyxoviridae
C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases