SummaryThis study investigates the influence on tromethamine (THAM) on ischemic volume induced by permanent middle cerebral artery occlusion (MCAO) in rats.14 male Sprague Dawley rats underwent left sided permanent MCAO by electro coagulation. Animals were treated either by 3-M THAM given intravenously in a single dosage of 0.6 mmol/kg body weight (THAM group: n = 7) 10 min following MCAO and again 1, 2, 3, 4 and 5 hours later or by NaCl 0.9% (placebo group: n = 7) in the same mode. Mean arterial blood pressure (MABP) was monitored for 30 min post MCAO and arterial blood gases were taken 10 min after the first injection. The extent of ischemia volume was assessed by planimetry of coronal sections stained with triphenyl-tetrazolium chloride (TTC) and with hematoxilin/eosin (HE). Tests for significance were accomplished by ANOVA on ranks. A difference of p < 0.05 was considered significant.The THAM group showed an insignificant decrease in MABP 1 min after injection (THAM: 75 ± 11 mmHg, placebo: 86 ± 10 mmHg). Arterial pH was significantly different (THAM: 7.46 ± 0.04; placebo: 7.32 ± 0.03). In TTC staining, the ischemia volume — given in absolute values and percentage of the total left volume — was significantly reduced in the THAM group (THAM: 43.9 ± 8.3mm3/7.0 ± 1.3%; placebo: 95.2 ± 13.8 mm3/14.2 ± 2.0%). In HE staining, the reduction of ischemia, volume did not reach statistical significance (THAM: 49.1 ± 9.9 mm3/9.6 ± 1.8%; placebo: 66.3 ± 14.5 mm3/13.1 ± 2.8%).Based on these results, a moderate neuroprotective effect of THAM in experimental cerebral infarction could be demonstrated.
SummaryMannitol is frequently used to reduce elevated intracranial pressure often associated with brain edema. In cases of a damaged blood-brain barrier, however, mannitol might aggravate vasogenic cerebral edema, as has recently been stressed. The aim of this study was to investigate whether multiple doses of mannitol administered during development of vasogenic brain edema following a cryogenic cortical injury affect hemispheric swelling and edema.Sprague-Dawley rats were anesthetized with ketamine and xylazine. A cortical freezing lesion was applied to the right parietal region. A first series of eight rats received four doses of 20% mannitol (0.4 g/kg within 10 minutes) thirty minutes, 3, 6 and 9 hours after trauma. Twelve hours after cryogenic injury, the brains were removed for determination of hemispheric swelling and cerebral water content. Eight control rats were infused with saline only.In a second series nine rats received eight doses of 20% mannitol 30 minutes, 3, 6, 9, 12, 15, 18 and 21 hours after trauma. In this series, the brains were removed 24 hours after freezing. Again respective control animals were infused with saline only.Hemispheric swelling was 7.2 ± 0.5% after four doses of mannitol compared to 7.6 ± 0,5% in control animals (n.s.). Following eight doses of mannitol hemispheric swelling was 8.9 ± 0.4% compared to 10.1 ± 0.4% in control rats (p < 0.05). Accordingly, the water content of traumatized hemispheres was lower following repeated mannitol treatment (80.5 versus 80.8%). Water content in control hemispheres was not affected by mannitol.Taken together, these results indicate that multiple doses of mannitol do not aggravate total hemispheric swelling, nor global water content following induction of vasogenic edema. In contrast, repeated administration of mannitol reduces traumatic swelling, thus favouring repeated mannitol application even when the blood-brain barrier is defective.
