Early surgery for ruptured cerebral arteriovenous malformations.

Acute surgery on cerebral arteriovenous malformations (AVMs) has seldom been reported or used. We reviewed 49 patients of ages 2 months to 78 years (mean 32.8 years), 32 male (65%) and 17 female (35%), treated acutely (within 4 days of bleed) in Helsinki Neurosurgery during 1997-2002. The following variables were assessed in regards to the outcome (Glasgow outcome score; GOS; 2-3 months after bleed): age, sex, Hunt and Hess Grade (HH), Spetzler-Martin Grade (SMG), location of AVM, size of intraparenchymal haematoma (ICH), and presence of intraventricular haemorrhage (IVH). Most of the patients were in a poor clinical condition on admission (two thirds were HH 4-5). 45 (92%) patients underwent extirpation of AVM and evacuation of ICH, within 4 days after bleed. Over 55% had good functional outcome. GOS correlated significantly with HH (p = 0.001), age (p = 0.006), and IVH (p = 0.049). On the other hand, SMG, location of AVM, and size of haematoma did not significantly predict the outcome. Microneurosurgery with preoperative embolization has made possible the excision of 90% of AVMs. It is our experience that it can be done acute and early, and it saves lives as compared to natural history of cerebral AVMs or late surgery, and accelerates rehabilitation of the patients.

Effects of dexmedetomidine after transient and permanent occlusion of the middle cerebral artery in the rat.

Increased sympathetic tone is a consequence of cerebral ischemia. Although the role of catecholamines in ischemic damage is still unclear, in some experimental ischemia models alpha2-adrenergic agonism has proved to be neuroprotective. In the present work we have compared the effects of transient and permanent middle cerebral artery occlusion (MCAO) on the infarct volume, and, also, examined whether a selective alpha2-adrenergic receptor agonist, dexmedetomidine (9 microg/kg or 15 microg/kg i.v.), is able to reduce ischemic damage after transient or permanent MCAO in rats. Permanent MCAO led to a significantly larger infarct volume than transient occlusion (p < 0.05). The rats receiving the higher dose of dexmedetomidine were detectected to have smaller (statistically non-significant) infarct volume in the cortex (30.9%) and in the striatum (20.3%) after transient occlusion. Additionally, dexmedetomidine caused significant variations in the physiological parameters.

The neuroprotective effects of (-)deprenyl in the gerbil hippocampus following transient global ischemia.

(-)Deprenyl (selegeline) is a monoamine oxidase B (MAO-B) inhibitor, but it also exerts several effects independent of MAO-B inhibition. For example, it has been shown to improve neuronal survival in different neurodegenerative models. In the present study, we have tested whether (-)deprenyl attenuates the neuronal damage in the hippocampus that is induced in a model of transient global ischemia in gerbils. (-)Deprenyl was administered 1) at a low daily dose starting two weeks before occlusion, 2) at a single high dose administered 3h after occlusion, or 3) at a low daily dose for one or two weeks after occlusion. A nonsignificant trend of reduced neuronal damage in the hippocampal CA1 area was seen in all experimental groups treated with (-)deprenyl, regardless of the timing of treatment. The results together with previous evidence suggest that (-)deprenyl may protect CA1 neurons from ischemia-induced delayed death by several possible mechanisms, including the suppression of oxidative stress and apoptotic processes.

Neuroprotective effects of dexmedetomidine in the gerbil hippocampus after transient global ischemia.

BACKGROUND: Cerebral ischemia induces a massive release of norepinephrine associated with neuronal death in the brain. It has been demonstrated that alpha2-adrenoceptor agonists decrease the release and turnover of noradrenaline, and this might prove advantageous in counteracting the neurodegeneration in ischemic brain. Therefore, in the present study, the authors tested whether dexmedetomidine, a selective alpha2-receptor agonist, has neuroprotective effects in a gerbil transient global ischemia model. METHODS: Ischemia was induced by bilateral carotid occlusion for 5 min in diethylether-anesthetized normothermic gerbils. Dexmedetomidine was administered subcutaneously in four different treatment paradigms (6-8 animals/group): 3 or 30 microg/kg 30 min before and thereafter at 3, 12, 24, and 48 h after the occlusion, or 3 or 30 microg/kg at 3, 12, 24, and 48 h after the occlusion. Control animals were subjected to forebrain ischemia but received only saline injections. One week after occlusion, animals were transcardially perfused for histochemistry. Neuronal death in the CA1 and CA3 regions of the hippocampus and in the hilus of the dentate gyrus was evaluated in silver-stained 60-microm coronal sections. RESULTS: Compared with saline-treated ischemic animals, dexmedetomidine at a dose of 3 microg/kg given before and continued after the induction of ischemia reduced the number of damaged neurons in the CA3 area (2 +/- 3 vs. 17 +/- 20 degenerated neurons/mm2; P < 0.05). Also in the dentate hilus, the number of damaged neurons was reduced by dexmedetomidine (3 microg/kg) given before and continued after ischemia (5 +/- 7 vs. 56 +/- 42 degenerated neurons/mm2; P < 0.01). CONCLUSIONS: The present data demonstrate that dexmedetomidine effectively prevents delayed neuronal death in CA3 area and in the dentate hilus in gerbil hippocampus when the management is started before the onset of ischemia and continued for 48 h after reperfusion. Inhibition of ischemia-induced norepinephrine release may be associated with neuroprotection by dexmedetomidine.

Decrease in brain choline-containing compounds following a short period of global ischemia in gerbils as detected by 1H NMR spectroscopy in vivo.

Cerebral metabolism was studied in the postischaemic gerbil brain using surface coil 31P and 1H NMR spectroscopy. The ratio of choline-containing compounds (Cho) to total creatine (Cr) in the brain decreased from 0.46 +/- 0.02 to 0.32 +/- 0.02 by the fifth day following exposure to 5 min of global ischaemia and it remained at this low level for at least 19 days. The amounts of cerebral Cho as quantified by 1H NMR in vivo were 1.70 +/- 0.15 and 1.09 +/- 0.22 mmol/kg in control and postischaemic animals, respectively. The T2 of Cho was longer in the postischaemic cerebral cortex than in the control one. N-acetyl aspartate (NAA) as determined by 1H NMR in vivo did not differ in the two animal groups. High-resolution 1H NMR of acid-extracted brain cortices showed a decrease in total Cho (glycerophosphocholine, phosphocholine and choline) by 31%, but no changes in NAA, total creatine, taurine and myo-inositol, in the brain cortex seven days postischaemia relative to control animals. The decrease in acid extractable Cho was mainly due to the drop in glycerophosphocholine concentration. 31P NMR indicated normal energy state and phosphomonoester/phosphocreatine (PCr) and phosphodiester/PCr ratios in the in vivo brain 7 days postischaemia. Silver impregnation did not reveal neuronal degeneration but immunohistochemical staining showed a number of glial fibrillary acidic protein expressing astrocytes as indicators of reactive gliosis in the postischaemic cerebral cortex. These data show, for the first time, that a 1H NMR decrease in Cho metabolites takes place as a consequence of brief ischaemic episode even in the absence of obvious neuronal degeneration.