{'fraction_non_alphanumeric': 0.029829545454545456, 'fraction_numerical': 0.015625, 'mean_word_length': 5.541795665634675, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Acute Disruption of Cytochrome Oxidase Activity in Brain in a Perinatal Rat Stroke Model

ABSTRACT: Cytochrome oxidase histochemistry in frozen brain sections provides an estimate of mitochondrial respiratory function and neuronal metabolic activity. We hypothesized that in a perinatal rodent stroke model acute selective disruption of cytochrome oxidase activity could identify neuronal populations susceptible to irreversible ischemic injury. In 7-d-old rats, focal ischemic injury was induced by right carotid ligation followed by 8% O2 exposure (2.75 h); this procedure elicits ipsilateral forebrain injury with prominent hippocampal lesions, often including dentate gyrus. Cytochrome oxidase activity was quantitated by densitom-etry in brain sections prepared from animals killed 1 h (n = 8), 24 h (n = 11), or 5 d (n = 3) posthypoxia. At 1 h posthypoxia, in six of eight there was diffuse ipsilateral suppression of cytochrome oxidase activity (p = 0.0001, two-way analysis of variance, compared with values in contralateral hemisphere), which was most marked in periventricular regions including dentate gyrus (−29%), medial habenula (−38%), and posterolateral thalamic nucleus (−42%). Nissl staining of adjacent sections was completely intact in four of eight, and four of eight had subtle focal reductions in staining. At 24 h and 5 d posthypoxia, heterogeneous suppression of cytochrome oxidase activity persisted in the lesioned hemisphere, with close anatomic correspondence between loss of cytochrome oxidase activity and loss of Nissl staining. Additional studies indicated that the threshold duration of 8% O2 exposure (after carotid ligation) for suppression of cytochrome oxidase activity was 1–2 h. Disruption of cytochrome oxidase activity represents one of the earliest detectable indicators of neuronal injury in this perinatal stroke model. The threshold duration of hypoxia to suppress its activity preceded or coincided with that to elicit injury, and the prominent loss of activity in dentate gyrus paralleled its enhanced susceptibility to ischemic injury at this developmental stage.