Correlation of morphologic brain lesions with physiologic alterations and blood-brain barrier impairment in 3-nitropropionic acid toxicity in rats.
3-Nitropropionic acid (NPA), a toxin which irreversibly inhibits the Krebs cycle enzyme succinate dehydrogenase, causes severe neurologic disease and a specific pattern of morphologic brain damage when given subcutaneously to rats. To determine whether hypotension or hypoxemia were necessary for development of morphologic brain lesions in NPA neurotoxicity, systemic blood pressure and arterial blood gases were measured in NPA-intoxicated rats. The extent and distribution of albumin extravasation was examined by immunohistochemistry, and was compared to the extent and severity of morphological injury in the caudate-putamen. Neither hypotension nor hypoxemia were necessary for the development of morphologic injury in the brains of NPA-intoxicated rats. In fact, intoxicated rats had significantly higher systolic blood pressure and arterial blood oxygen than did controls. Arterial bicarbonate and pH were significantly lower in intoxicated rats than controls, however, suggesting that acidosis may be involved in the pathogenesis of NPA toxicity. When morphologic injury was severe, albumin extravasation was extensive occupying approximately 30%-80% of the lesion area in the caudate-putamen of NPA-intoxicated rats. When morphologic injury was mild, albumin extravasation was absent, or limited to small cuffs around individual capillaries (less than 1% of the lesion area). There was no leakage of albumin in the cerebral cortex, which was resistant to morphologic injury. It was concluded that leakage of protein-rich fluid into cerebral parenchyma from blood-brain barrier impairment is not responsible for the initiation of morphologic injury in NPA toxicity, but may contribute to the severity of injury later in the evolution of brain lesions.
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002245:Carbon Dioxide / Q000097:blood; D007279:Injections, Subcutaneous; D008297:Male; D009574:Nitro Compounds; D010100:Oxygen / Q000097:blood; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D000418:Albumins; D009574:Nitro Compounds; D011422:Propionates; D002245:Carbon Dioxide; C015392:3-nitropropionic acid; D010100:Oxygen