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The effect of GM1 ganglioside treatment on the recovery of biochemical and behavioral parameters which define the activity of nigro-striatal dopaminergic systems has been investigated in rats after different types of lesion. GM1 favours the recovery of tyrosine-hydroxylase activity, of the number and affinity of 3H-N-n-propyl-norapomorphine binding sites in the striatum of the lesioned side and reduces the apomorphine-induced rotational behavior after mechanical (i.e. unilateral hemitransection) but not after chemical (i.e. 6-OHDA injected in the substantia nigra) lesion. The source of regrowing dopaminergic nerve terminals in the striatum after hemitransection is mainly a response of intact remaining axons of the ipsilateral side. Moreover the contralateral nigro-striatal systems seems to play, through intrathalamic connections, an important role in regulating the GM1-induced increase of the tyrosine-hydroxylase activity.

Stimulation of inositol phospholipid hydrolysis by transmitter receptor agonists was measured in slices from hippocampus, cerebral cortex, and corpus striatum at various intervals after transient global ischemia in rats. Ischemia was induced through the four-vessel occlusion model. Stimulation of [3H]inositol monophosphate formation by excitatory amino acids was greatly enhanced in hippocampal slices prepared from ischemic rats at 24 h or 7 days after reperfusion. This potentiation was more evident using ibotenic acid and was also observed in cerebral cortex, but not in corpus striatum. This regional profile correlated with the pattern of ischemia-induced neuronal damage observed under our experimental conditions. The enhanced responsiveness to excitatory amino acids was always accompanied by an increase in both basal and norepinephrine-stimulated [3H]inositol monophosphate formation. In contrast, stimulation of [3H]inositol monophosphate formation by carbamylcholine was not modified in hippocampal or cortical slices from ischemic animals.

We assessed the consequences of transitory global cerebral ischemia and the influence of monosialoganglioside inner ester (AGF 2) treatment on neurologic outcome, cerebral blood flow, and cerebral metabolic rate in monkeys over 48 hours. Global cerebral ischemia was produced by a cervical tourniquet and a lowering of blood pressure to 6.65 kPa; recirculation followed after 30 minutes. AGF 2 (30 mg/kg) was administered intravenously immediately after initiation of recirculation and intramuscularly twice a day for 48 hours. Our results show that treatment with AGF 2 significantly accelerated the rate of neurologic recovery. Improvement was evident 5 hours after ischemia; full neurologic recovery was observed in half of the monkeys 48 hours after ischemia. This recovery was associated with a less severe reduction in cerebral blood flow without a concomitant increase in the cerebral metabolic rate. (Stroke 1989; 20:652-656) G angliosides are sialic acid-containing glycosphingolipids with particular abundance in the outer membrane surface of neuronal cells.' Although their biologic function is still largely obscure, considerable evidence now indicates that systemically administered gangliosides are effective in improving the outcome following neuronal injury to adult rodents. In the initial work of Ceccarelli et al, 2 a mixture of bovine brain gangliosides enhanced recovery of the denervated cat nictitating membrane, an effect most probably associated with an enhanced rate of axonal regrowth.3 Subsequently, the monosialoganglioside GM 1 (nomenclature according to Svennerholm 4 ) alone was found to affect recovery following injury to the central nervous system (CNS). For example, following partial unilateral hemitransection of the nigrostriatal pathway, chronically administered GM 1 facilitated the recovery of dopaminergic synaptic function in the lesioned striatum.5 This effect was associated with both enhanced survival of nigral dopaminergic cell bodies and with the associated reduction of the imbalance in energy metabolism and blood flow between the striata of the lesioned and unlesioned sides. Received March 4, 1988; accepted October 18, 1988. GM 1 effects have also been detected during the acute phase following brain insults, including cerebral ischemia. GM 1 treatment has been shown to have beneficial effects following both transitory middle cerebral artery occlusion in cats and permanent unilateral ligation of the common carotid artery in gerbils. -9We describe the effects of AGF 2, the inner ester derivative of GM 1, following transitory global cerebral ischemia in monkeys. We used AGF 2 because of its reportedly greater ability to penetrate the blood-brain barrier. 10 Materials and MethodsWe used 27 cynomolgus monkeys {Macaca fascicularis) of either sex weighing 3-6 kg. Anesthesia was induced with 3 mg/kg i.m. ketamine hydrochloride followed by an intravenous perfusion of 25 mg/kg chloralose. The monkeys were intubated and then ventilated (Delhomme, Bird Mark 8, Paris, France) so as to maintain Pacc>2 at 5...