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Effect of mannitol on experimental focal ischemia in awake monkeys
Abstract:
The effect of mannitol on focal cerebral ischemia in cynomolgus monkeys was studied. After the implantation of a snare ligature about the right middle cerebral artery (MCA) and of deep electrodes for measurement of cerebral blood flow, unanesthetized animals underwent 4-hour MCA occlusion. Ten monkeys were untreated, and 12 animals received mannitol (1.2 g/kg i.v.) 20 minutes after occlusion. The preocclusion and postocclusion deep hemispheric cerebral blood flows (mean CBFs) were similar in the treated and untreated groups. Occlusion produced an average decrease in flow of about 50% in both groups. In the mannitol-treated group the mean CBF of 30.0 fell to 15.8 ml/100 g/minute, and in the untreated group the mean CBF of 29.5 fell to 12.5 ml/100 g/minute. Several animals showed increased CBF after mannitol treatment, and there was an average 21% increase in CBF in the mannitol group after treatment, but this was not a statistically significant difference from the untreated group. With regard to clinical status, there was no significant difference between the mannitol group and the untreated group after MCA occlusion. In individual animals, mannitol treatment caused no significant improvement. Two weeks after occlusion, brains were evaluated for infarct size; there was no significant difference between the mannitol and the untreated groups. In this study, treatment with mannitol (1.2 g/kg) 20 minutes after MCA occlusion failed to modify significantly the mean hemispheric CBF, clinical status, or the pathological effects of 4-hour focal cerebral ischemia.
Insights
Mannitol treatment did not significantly improve cerebral blood flow or reduce brain damage in cynomolgus monkeys experiencing focal cerebral ischemia. This study found no significant benefits from mannitol in treating middle cerebral artery occlusion.
Area of Science:
- Neuroscience
- Pharmacology
- Medical Research
Background:
- Focal cerebral ischemia, often caused by middle cerebral artery (MCA) occlusion, leads to significant neurological deficits.
- Mannitol is a hyperosmotic agent sometimes used to reduce intracranial pressure and edema in neurological conditions.
Purpose of the Study:
- To investigate the therapeutic effect of mannitol on focal cerebral ischemia in a primate model.
- To assess mannitol's impact on cerebral blood flow, clinical status, and infarct size following MCA occlusion.
Main Methods:
- Cynomolgus monkeys underwent 4-hour MCA occlusion with or without intravenous mannitol treatment (1.2 g/kg) administered 20 minutes post-occlusion.
- Cerebral blood flow (CBF) was measured using deep electrodes before and after occlusion.
- Clinical status and infarct size (2 weeks post-occlusion) were evaluated to determine treatment efficacy.
Main Results:
- Mannitol treatment did not significantly alter mean hemispheric cerebral blood flow compared to the untreated group.
- No statistically significant improvement in clinical status or reduction in infarct size was observed in the mannitol-treated group.
- While some animals showed a transient increase in CBF after mannitol, this effect was not statistically significant.
Conclusions:
- Mannitol administration at 1.2 g/kg, 20 minutes after MCA occlusion, failed to provide significant therapeutic benefits in this primate model of focal cerebral ischemia.
- The findings suggest that mannitol may not be effective in mitigating the acute or long-term consequences of MCA occlusion in this experimental setting.