Middle cerebral artery occlusion in the rat: consistent protocol for a model of stroke

Variability in the effects of the intraluminal suture method of middle cerebral artery occlusion (MCAO) in the rat has been a common and disadvantageous finding. Therefore, we systematically investigated the effects of suture type and rat strain on outcome. First, the clinical and neuropathological effects of permanent MCAO with either an uncoated or a silicone-coated nylon suture were studied over 7  days in Sprague–Dawley rats ( n =36 for each type of suture). Outcome was less severe with the uncoated compared with the silicone-coated suture (e.g. total cerebral infarct volume at 24  h before any fatalities was 119.9±79.8  mm³ , cf. 183.0±36.5 mm³ , n =12 for each, P <0.05; and overall mortality rate was 12.5% cf. 33%, respectively), but much more variable (coefficient of variation was 66.6% cf. 19.9%, respectively). Second, being more consistent in its effects, the silicone-coated suture was further studied in Wistar and Fischer-344 rats ( n =12 for each). Seventy-five per cent of the Wistar's died prematurely from gross hemispheric oedema. Motor deficit and extent of infarction in the Fischer-344 rats were both significantly greater compared with Sprague-Dawley rats (e.g. total cerebral infarct volume at 24  h in the former was 253.6±25.4  mm³ , n =11, P <0.05), and more consistent (coefficient of variation was only 10.0%). It was concluded that the silicone-coated suture and the Fischer-344 rats strain produced the most consistent results and their novel combination provides a reliable acute stroke model.     

The evolution and distribution of morphological changes in the nervous system of the common marmoset following the acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Six young adult marmosets received 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in multiple doses (total 8-16 mg/kg over 2-13 days) sufficient to produce a parkinsonian syndrome and were killed up to 3.5 months later. Cellular changes were found in the substantia nigra, ventral tegmental area, and hypothalamus. The earliest histological abnormalities were axonal swellings in proximal parts of nigrostriatal axons. Subsequent changes in the substantia nigra were reduced Nissl staining, reduced cell volume, and aggregation and loss of melanin granules. Other effects were reduced nuclear and nucleolar volumes, depletion of cells, and hyperplasia of glial cells. Shrunken cytoplasm and nuclei stained uniformly with eosin, and no cells showed cytoplasmic swellings or inclusions. These cellular alterations, with nuclear changes resembling karyolysis, do not occur in Parkinson's disease, which is characterised by Lewy body inclusions and signs of chromatolysis. The rapid appearance of axonal swellings, disruption of Nissl substance, and cell shrinkage suggest an insult to energy producing mechanisms. In this study, the absence of histological evidence of toxicity in the locus coeruleus and also in the substantia innominata and in serotonergic cell groups is unlike the more widespread degenerative changes of Parkinson's disease.     

Temporary middle cerebral artery occlusion in the rat: consistent protocol for a model of stroke and reperfusion

The intraluminal suture method of middle cerebral artery occlusion (MCAO) in the rat (the suture model) is a model of stroke which readily lends itself to studying the pathophysiology of post-ischaemic reperfusion. Unfortunately, variability of outcome has compromised the potential of the model, but systematic studies might characterize a consistent protocol. Therefore, the clinical and neuropathological outcome of temporary MCAO and reperfusion in the suture model were systematically investigated. Two hours or 4 h of MCAO were employed, measuring the extent of infarction at 24 h with triphenyltetrazolium chloride or at 72 h with histopathological techniques. Outcome was compared in three rat strains. Following 2 h of MCAO, motor function improved during reperfusion in Sprague-Dawley, but not in Wistar or Fischer-344 rats. All Sprague-Dawley and Wistar rats survived the protocol to 72 h, but 33% of Fischer-344 rats died. The extents of infarction and oedema were greater and less variable in Wistar and Fischer-344 than Sprague-Dawley rats, and in all three strains, the extent of infarction increased with reperfusion time. Following 4 h of MCAO, there was no improvement in motor function during reperfusion in Sprague-Dawley rats, and mortality was high at 24 h in Wistar (33%) and Fischer-344 rats (83%). Outcome was only pursued in Sprague-Dawley rats to 72 h, where the extent of infarction was quite variable. It was concluded that the extent and variability of outcome following temporary MCAO in the suture model is strain-dependent, and a consistent protocol with zero mortality was found in Wistar rats using 2 h of MCAO and 70 h of reperfusion.