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Biomedical subjects

M Grabowski

Publications and source records attributed to M Grabowski.

At least 37 records · Page 2Linked to original sources
PubMed1994

Capsaicin-induced gastric hyperemia and protection are NO- dependent.

Topical treatment of gastric mucosa with capsaicin (cap) increases gastric mucosal blood flow (GMBF) and protects the mucosa from injury by acidified bile salts. The purpose of this study was to test the hypothesis that this hyperemia related "cytoprotection" is mediated by nitric oxide. Male Sprague-Dawley rats were anesthetized and the glandular stomach (blood supply intact) was chambered between two plastic rings. Animals were divided into four groups. All groups received a 5-min topical saline exposure. Groups 1 and 2 received iv saline or nitro-L-arginine methyl ester (L-NAME, 25 mg/kg iv), a specific nitric oxide inhibitor, 5 min prior to baseline treatment, followed by a 15-min preinjury period of saline and a 15-min injury period of 10 mM acidified taurocholate (ATC, pH 1.2). Groups 3 and 4 were treated as above except topical cap (160 microM) was used during the preinjury period. GMBF was measured with a laser Doppler flowmeter (ml/min/100 g tissue). Injury was assessed grossly (grade 0-3), histologically (grade 0-3), and by measuring DNA content of a 5-min N-acetylcysteine wash (DNAE). Baseline GMBF of 30 +/- 1.5 significantly decreased to 15 +/- 1.2 in group 1 versus group 2 (P < 0.05). When topical ATC was used GMBF increased to 59 +/- 4.9 and 25 +/- 2.8, respectively. Injury by grade and DNAE was not significantly different between these groups. GMBF during cap exposure was 42 +/- 4 and 22 +/- 2 in groups 3 and 4, respectively. Graded histologic and gross injuries were significantly worse in group 4 compared to group 3 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Functional recovery after brain infarction: plasticity and neural transplantation.

In the past, little attention has been given to the role of brain plasticity for the long term functional outcome in experimental stroke although there is substantial evidence for plasticity in other experimental models of neurological disorders. Under clinical conditions, functional improvement occurs in most stroke survivors during the initial months after the ischemic incidence. Recent PET studies in stroke patients, investigated two months or later after stroke, indicate a considerable potential for functional plasticity in the adult human cerebral cortex. Research aimed at the identification of the mechanisms underlying functional recovery should be given high priority, particularly with regard to environmental factors and pharmacological interventions. Pilot experiments of environmental enrichment significantly improved the functional outcome of laboratory animals after brain infarction. Fetal neocortical tissue grafted into the infarcted area in adult rats received afferent fibres from the intact brain and responded to contralateral sensory stimulation with increased metabolic activity, indicating functional integration between neocortical grafts and host afferent systems. However, reciprocal connections from the graft to the host tissue were rare, and it remains to be shown whether grafting will be able to restore the complex cortical organization of the infarcted tissue.

Adrenergic alpha-Agonists↗
PubMed1993

Functional integration of cortical grafts placed in brain infarcts of rats.

Five to 6 days after a right middle cerebral artery occlusion, a cell suspension of fetal neocortex was grafted into the infarcted area of adult spontaneously hypertensive rats. Three to 17 months later, functional integration of the grafts into the afferent somatosensory pathway was tested using the 2-[14C]deoxyglucose method for estimation of glucose utilization. Grafted rats (n = 8) and control rats (n = 5) with no arterial occlusion were stimulated in the left vibrissal region resulting in an increased glucose utilization in the left trigeminal sensory nucleus and the right ventroposterior nucleus of the thalamus, whereas the same regions in a group (n = 5) of nonstimulated grafted rats were not activated. Glucose uptake in the right somatosensory cortex of control rats was 96 +/- 5 (mean +/- SEM) mumol/100 gm/min. Neocortical grafts consumed less glucose than cortex in control rats but the vibrissae-stimulated group displayed a 110% higher value than the nonstimulated grafted group (32 +/- 5 vs 15 +/- 2, p < 0.05). We conclude that graft glucose metabolism is increased following stimulation of the host somatosensory pathway, which demonstrates that transplanted neurons can be functionally integrated with neural circuitries of the host after an ischemic insult.

Animals↗
PubMed1993

Cerebral blood flow in patients with severe hypertension, and acute and chronic effects of felodipine.

OBJECTIVES: To evaluate whether a spontaneous increase in cerebral blood flow (CBF) could be observed in subjects with severe hypertension and to study the effect of a calcium antagonist, felodipine, on blood pressure and CBF after acute and chronic administration. DESIGN: Patients with severe hypertension were recruited at the emergency ward. Patients with previous treatment with calcium antagonists, women of child-bearing potential, severe uraemia, nephrotic syndrome, heart failure, manifest cerebrovascular lesions and pathological liver function tests were excluded. METHODS: CBF was measured by single-photon emission computed tomography after intravenous administration of xenon-133 before (CBF1) and after intravenous infusion of felodipine, 0.01 mg/min during 40-60 min (CBF2) in 12 patients aged 25-67 years with no antihypertensive treatment except for beta-blockers in four patients and beta-blockers plus a diuretic in one patient. CBF was repeated after 3 weeks of oral therapy with felodipine, 5-10 mg twice a day with the addition of beta-blockers in 10/12 patients (CBF3). RESULTS: During the felodipine infusion blood pressure decreased. There were no neurological symptoms or signs before or during the felodipine administration. CBF1 was within normal limits with no significant differences between previously treated and untreated patients. There was a non-significant tendency to increase in global CBF after felodipine administration, associated with a significant reduction in the physiological side differences in blood flow. CONCLUSIONS: In spite of the initially very high blood pressure, no general or focal hyperaemia was observed, and thus no evidence for a 'breakthrough' of the cerebral autoregulation. Felodipine gives a smooth blood pressure reduction with a maintained CBF.

Adult↗
PubMed1993

Brain capillary density and cerebral blood flow after occlusion of the middle cerebral artery in normotensive Wistar-Kyoto rats and spontaneously hypertensive rats.

OBJECTIVE: In order to elucidate why spontaneously hypertensive rats (SHR) develop larger brain infarcts distal to an arterial occlusion than normotensive Wistar-Kyoto (WKY) rats, we determined the surface and volume densities of cerebral capillaries, and the regional cerebral blood flow distal to an arterial occlusion in SHR and WKY rats. DESIGN: Occlusion of the middle cerebral artery was chosen because the middle cerebral artery territory is most commonly affected by cerebral infarcts in man. METHODS: Surface and volume densities of capillaries in the neocortex of the middle cerebral artery territory were measured by stereological techniques on histological sections. Fifteen minutes after ligation of the right middle cerebral artery, regional cerebral blood flow was measured autoradiographically by the [14C]-iodoantipyrine method. RESULTS: The capillary density of the neocortex did not differ between the SHR and WKY rats. The blood flow was significantly lower within the middle cerebral artery territory in the SHR than in the WKY rats. CONCLUSIONS: The reduced blood flow distal to the occlusion in SHR is probably a consequence of structural adaptation of arterial resistance vessels, rather than being caused by reduced capillary density.

Animals↗
PubMed1993

Paw-reaching, sensorimotor, and rotational behavior after brain infarction in rats.

BACKGROUND AND PURPOSE: Functional tests that are stable and consistent over time are an advantage for long-term evaluation of treatment in experimental stroke research. Because little information on this subject is available in rodents with focal cerebral ischemia, we investigated the outcome of three behavioral tests for a period of 3 months after the insult. METHODS: Spontaneously hypertensive rats were sham-operated (n = 27) or underwent an occlusion (n = 36) of the right middle cerebral artery. Before surgery all rats were tested for amphetamine-induced rotational behavior, and half of the rats were trained in a paw-reaching task. One, 2, and 3 months after surgery the tests were repeated, together with a test for sensorimotor function. Infarct size was measured morphometrically. RESULTS: In the lesion group, total hemisphere area was reduced by 22%, caudate putamen by 47%, and the thalamus by 24%. Contralateral to the lesion, paw-reaching was highly impaired, regardless of whether or not the rats had been pretrained, and lesion size correlated significantly to paw-reach performance. Ipsilateral rotation increased and sensorimotor function recovered with time in infarcted rats. CONCLUSIONS: In contrast to amphetamine-induced rotation and sensorimotor behavior, the paw-reaching test provides a stable behavioral parameter after a middle cerebral artery occlusion. Moreover, the lesion-induced deficit in paw-reaching is highly correlated to the extent of the infarct, suggesting that this test is useful in evaluating treatment effects for a longer period of time.

Amphetamine↗
PubMed1992

Fetal neocortical grafts implanted in adult hypertensive rats with cortical infarcts following a middle cerebral artery occlusion: ingrowth of afferent fibers from the host brain.

This study is focused on the survival of fetal neocortical grafts placed in the infarcted adult host cortex of the spontaneously hypertensive rat and describes the ability of host axonal regeneration into the graft after a focal ischaemic lesion. Five to seven days following ligation of the right middle cerebral artery, dissociated neocortical primordium from fetuses of gestational age 12-18 days was implanted into the infarcted cortical area. Surviving transplants were seen in all rats, although grafts derived from gestational age 12-14 days displayed an irregular morphology rich in sinusoid-like cavities and containing fewer cells of apparently mature neuronal morphology. Grafts from older donors contained perikarya of neuronal appearance; however, they lacked normal cortical lamination. Ten days postgrafting, fibers stained by acetylcholinesterase histochemistry, dopamine-beta-hydroxylase, and 5-hydroxytryptamine immunohistochemistry were found in the grafts, and by 10-23 weeks after transplantation the fiber density had increased substantially. When the retrograde tracer Fluoro-Gold was injected into the grafted tissue, labeled cells were found in several subcortical nuclei of the host, including the nucleus basalis of Meynert, ventral pallidum, thalamus, dorsal raphe, locus coeruleus, as well as the ipsilateral and contralateral neocortex. This study shows that grafts of dissociated neocortical tissue exhibit good survival and growth potential when implanted into infarcted neocortex and that several nerve fiber systems of the adult host have a regenerative capacity sufficient to innervate the grafted tissue.

Acetylcholinesterase↗
PubMed1992

Vascularization of fetal neocortical grafts implanted in brain infarcts in spontaneously hypertensive rats.

The vascularization of neural grafts in ischemic brain was studied in spontaneously hypertensive rats grafted with a suspension of fetal neocortical tissue into the infarcted area five to six days after ligation of the middle cerebral artery. The brain vasculature was examined by scanning electron microscopy of corrosion vascular casts and the cortical microvasculature was stereologically quantified in light microscopy three months after the occlusion. Patent anastomoses were present between the middle cerebral artery distal to occlusion and the proximal part, as well as to the anterior and posterior cerebral arteries, in both grafted and non-grafted rats. A vascular plexus covering the infarct cavities and the grafts contained leptomeningeal vessels intermingled with a thin capillary network which is not normally found on the brain surface. The graft vessels were derived from this vascular plexus. The regular pattern of arterioles and venules penetrating from the cortical surface in normal neocortex was absent in the grafts but the capillary morphology was similar in both types of tissue. The grafts had a lower capillary density than normal tissue and lacked the laminar distribution of capillaries characteristic of normal neocortex. The results demonstrate the plasticity of the vascular system where remodeling of the vascular tree after an ischemic insult provides suitable conditions for the vascularization of neocortical grafts.

Animals↗
PubMed1991

Sensorimotor performance and rotation correlate to lesion size in right but not left hemisphere brain infarcts in the spontaneously hypertensive rat.

In order to correlate behavioural deficits to lesion size and to reveal possible functional asymmetries in the rat brain, locomotor activity, rotation and sensorimotor integration to touch were studied in spontaneously hypertensive rats (SHR) subjected to right or left middle cerebral artery occlusion. Control and infarcted rats showed no difference in locomotor activity. Infarcted rats tended to rotate towards the side of the lesion. A large sensorimotor deficit was found contralateral to the infarcted hemisphere. The absolute values of the side-biases for the rotation and sensorimotor tests were of the same degree irrespective of lesion side. Whereas the left hemisphere lesion size did not correlate to the behavioural outcome, the size of the right hemisphere lesion was highly correlated to the total sensorimotor deficit. Furthermore, the sensorimotor deficit of specific body parts was found to correlate to the damage of certain brain regions in a rostrocaudal fashion, reminiscent of a somatotopical organization. The extent of ipsilateral rotation correlated to brain tissue loss at the level of the posterior caudate-putamen. The present results indicate an asymmetrical organization for brain functions involved in the performance of the rotation and sensorimotor tests.

Animals↗
PubMed1988

Middle cerebral artery occlusion in the hypertensive and normotensive rat: a study of histopathology and behaviour.

Brain infarct size and behaviour were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) 3 weeks after occlusion of the right middle cerebral artery in order to compare the effects of vascular occlusions on the normotensive and hypertensive cerebral vasculature. The brain tissue reduction, assessed by measuring the cross-sectional area of remaining tissue and weight of the cerebral hemispheres, was greater in SHR than in WKY (P less than 0.01). Deficits in sensorimotor integration were highly correlated to the degree of brain damage (r = 0.91). Amphetamine induced no rotation asymmetry in normal rats, whereas lesioned rats rotated more ipsilaterally to the lesion (P less than 0.05). Rotation asymmetry did not correlate with total infarct size. The more severe outcome after middle cerebral artery occlusion in SHR as opposed to WKY, can probably be explained by reduced collateral capacity secondary to the altered vascular design in hypertension.

Animals↗