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Biomedical subjects

S Rehncrona

Publications and source records attributed to S Rehncrona.

At least 37 records · Page 2Linked to original sources
PubMed1992

Transplantation of fetal dopamine neurons in Parkinson's disease: PET [18F]6-L-fluorodopa studies in two patients with putaminal implants.

Two patients with Parkinson's disease who underwent implantation of fetal mesencephalic tissue into the putamen were serially studied using positron emission tomography and [18F]6-L-fluorodopa ([18F]dopa). The uptake of [18F]dopa is related to the functional integrity of the presynaptic dopaminergic system. Preoperative studies revealed a marked decrease in putamen [18F]dopa uptake, with lesser involvement of the caudate. Two and 4 months, respectively, after operation, both patients demonstrated functional improvement, as described elsewhere. One patient was scanned 5, 8, and 13 months after the operation and the other was scanned 7 and 12 months after the operation. In both patients, [18F]dopa uptake increased within the operated putamen despite a progressive decrease in tracer uptake in the unoperated striatal structures. We believe that this increased uptake of [18F]dopa at the implantation site represents functional integrity within a surviving neural graft. While there has been little further clinical improvement beyond the fifth postoperative month, the uptake of [18F]dopa at the operation site in both patients has progressively increased. The kinetic data provide evidence of disease progression in the unoperated striatum, which, balanced against increasing graft function, may explain why clinical improvement reached a plateau within months after surgery.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease.

Neural transplantation can restore striatal dopaminergic neurotransmission in animal models of Parkinson's disease. It has now been shown that mesencephalic dopamine neurons, obtained from human fetuses of 8 to 9 weeks gestational age, can survive in the human brain and produce marked and sustained symptomatic relief in a patient severely affected with idiopathic Parkinson's disease. The grafts, which were implanted unilaterally into the putamen by stereotactic surgery, restored dopamine synthesis and storage in the grafted area, as assessed by positron emission tomography with 6-L-[18F]fluorodopa. This neurochemical change was accompanied by a therapeutically significant reduction in the patient's severe rigidity and bradykinesia and a marked diminuation of the fluctuations in the patient's condition during optimum medication (the "on-off" phenomenon). The clinical improvement was most marked on the side contralateral to the transplant.

Brain↗
PubMed1989

Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up.

By using stereotaxic surgical techniques, ventral mesencephalic tissues from aborted human fetuses of 8 to 10 weeks' gestational age were implanted unilaterally into the striata in two patients with advanced Parkinson's disease. The patients were treated with a cyclosporine, azathioprine, and steroid regimen to minimize the risk for graft rejection. They were examined for 6 months preoperatively and 6 months postoperatively and continued to receive the same doses of antiparkinsonian medication. There were no significant postoperative complications. No major therapeutic effect from the operation was observed. However, in the clinical tests, both patients showed small but significant increases of movement speed for repeated pronation-supination, fist clenching, and foot lifting. The rate of walking also increased in the one patient tested. For both patients, there was an initial worsening postoperatively, followed by improvement vs preoperative performance at 1 to 3 months. Both patients also showed significant improvement in the magnitude of response to a single dose of levodopa (L-dopa), but there was no increase in the duration of drug action. The motor readiness potential increased in both patients postoperatively, primarily over the operated hemisphere. Neurophysiological measurements also showed a more rapid performance of simple and complex arm and hand movements on the side contralateral to transplantation in one patient at 5 months postoperatively. Positron emission tomography demonstrated no increased uptake of 6-L-(18F)-fluorodopa in the transplanted striatum at 5 and 6 months. Taken together, these results suggest that the fetal nigral implants may have provided a modest improvement in motor function, consistent with the presence of small surviving grafts. Although our results support further scientific experimentation with transplantation in Parkinson's disease, widespread clinical trials with this procedure are probably not warranted at this time.

Contingent Negative Variation↗
PubMed1989

Enhancement of iron-catalyzed free radical formation by acidosis in brain homogenates: differences in effect by lactic acid and CO2.

The influence of lactic acidosis and of extreme hypercapnia on free radical generation and lipid peroxidation in brain tissues was studied. Cortical homogenates were prepared from the rat brain in a bicarbonate buffer and incubated for 60 min. Lipid peroxidation was evaluated by measurements of thiobarbituric acid reactive (TBAR) material and alpha-tocopherol analysis. The pH during incubations were decreased to 6.10-6.20 by either lactic acid administration or equilibration with 60% CO2 gas in paired experiments. In homogenates treated with lactic acid there was a 20-fold increase in TBAR material and the alpha-tocopherol concentration decreased to approximately 60% of control. There was only a 10-fold increase in TBAR material and no change in alpha-tocopherol concentration if acidosis was induced by CO2. These differences between lactic acidosis and hypercapnic acidosis were statistically highly significant. The results indicate that lactic acidosis has a more pronounced effect in augmenting free radical generation in brain tissues than acidosis due to an increase in CO2 tension. It is suggested that this effect of lactic acid is mediated by increased dissociation of catalytic iron from proteins of the transferrin type.

Acidosis, Lactic↗
PubMed1986

Molecular mechanisms for ischemic brain damage and aspects on protection.

Multiple factors are responsible for the development of irreversible cell damage in the ischemic brain. Different molecular mechanisms may operate alone or may influence each other to create a vicious circle leading to a point of no-return. Tissue energy failure, disruption of ionic homeostasis, and severe tissue lactic acidosis can be regarded as major basic mechanisms that provoke a sequence of events finally leading to degradation and death of brain cells. Accumulation of calcium, liberation of free fatty acids, and pathologic free radical reactions during the postischemic phase may have additional pathogenetic significance. Possibilities to protect the ischemic brain are discussed with respect to the different pathogenetic mechanisms. Primarily, these include measures taken to decrease the cerebral energy demands and to prevent the development of severe tissue lactic acidosis.

Acidosis, Lactic↗
PubMed1985

Effect of different degrees of brain ischemia and tissue lactic acidosis on the short-term recovery of neurophysiologic and metabolic variables.

The recovery of the EEG and somatosensory evoked responses (SER) as compared with recovery of the cerebral energy state was studied in rats during recirculation following different degrees of brain ischemia with varying tissue lactic acidosis. Reversible complete and incomplete ischemia was induced either by increasing the intracranial pressure (compression ischemia) or by carotid artery clamping combined with arterial hypotension. In incomplete ischemia the degree of tissue lactic acidosis was varied by manipulations of blood and brain glucose levels. Animals with an increase in brain lactate to about 25 mumol X g-1 (whole brain wet weight) during ischemia showed persistent failure of both cerebral energy metabolism and neurophysiologic restitution during the recirculation phase; if less than 20 mumol X g-1 metabolic recovery was almost complete. Despite a similar restitution of tissue energy metabolism in these animals, neurophysiologic recovery was inversely proportional to brain lactate concentrations during ischemia. At similar levels of ischemic tissue lactic acidosis, and despite a similar recovery of cortical energy state, the neurophysiologic restitution was clearly inferior after complete ischemia to that following incomplete ischemia. Three conclusions were drawn: (i) neurophysiologic variables were more sensitive indicators of postischemic persistent cerebral dysfunction than the cerebral energy state; (ii) the degree to which lactate accumulated in the ischemic brain influenced neurophysiologic restitution even if concentrations critical for metabolic recovery were not attained; and (iii) incomplete ischemia was less harmful than complete ischemia provided that tissue lactic acidosis was not excessive.

Acidosis↗
PubMed1985

Brain acidosis.

Brain tissue acidosis is a result of either an increase in tissue PCO2 or an accumulation of acids produced by metabolism. Severe hypercapnia (arterial PCO2 around 300 mm Hg) may cause a fall in tissue pH to around 6.6 without any deterioration of the cerebral energy state or morphologic evidence of irreversible cell damage. In severe ischemia and tissue hypoxia, anaerobic glycolysis leads to lactic acid accumulation. This is aggravated by hyperglycemia and by a (trickling) residual blood flow. Under such circumstances lactate concentration in the tissue may increase to levels above 20 to 25 mumol/g (tissue wet weight), causing a decrease in pH to around 6.0. If lactic acidosis during ischemia or hypoxia reaches these excessive levels, metabolic and functional restitution is severely hampered upon subsequent recirculation and reoxygenation. In these circumstances cell morphology shows signs of irreversible damage. Conversely there is less damage if severe tissue lactic acidosis can be hindered. The deleterious effect of excessive lactic acidosis may be related to an influence on the following: synthesis and degradation of cellular constituents; mitochondrial function; cell volume control; postischemic blood flow; and stimulation of pathologic free radical reactions. Possibilities for therapeutic interventions include the avoidance of hyperglycemia, inhibition of glycolysis, and measures for increasing the buffer capacity of the brain.

Acidosis↗
PubMed1985

Diagnosis of brain abscesses with indium-111-labeled leukocytes.

Sixteen patients with intracerebral mass lesions where computed tomography (CT) was not fully conclusive with respect to the differential diagnosis between brain tumor and abscess were examined with leukocyte brain scintigraphy (LBS). Autologous leukocytes were labeled with indium-111 oxinate and were reinjected intravenously; registration with a gamma camera was performed after 24 and 48 hours. In 10 of 11 patients with the final diagnosis of a brain tumor, no accumulation of radiolabeled leukocytes could be detected in the brain. In 4 of 5 patients with the final diagnosis of brain abscess, scintigraphy showed a pronounced increase of focal activity corresponding to the lesion demonstrated with CT. The reasons for the one false-positive and the one false-negative result are discussed, and it is concluded that LBS (a) can be used to detect intracranial infection and (b) may be a useful diagnostic tool for distinguishing between brain abscess and brain tumor.

Adult↗
PubMed1983

Brain lactic acidosis and ischemic cell damage: quantitative ultrastructural changes in capillaries of rat cerebral cortex.

Excessive tissue lactic acidosis has earlier been shown to aggravate structural damage of both neurons and glial cells in the rat cerebral cortex. To study the reactions of cortical capillaries, light- and electronmicroscopic morphometry was used. Rats were subjected to severe incomplete ischemia (cerebral blood flow below 5% of normal) for 30 min by clamping their carotid arteries and by lowering the blood pressure. Lactate production during ischemia was modified by preischemic administration of either saline (low lactic acidosis group) or glucose (high lactic acidosis group). In the animals with low lactic acidosis, only minimal vascular changes were seen after both 5 min and 90 min recirculation. In the high lactic acidosis group, the endothelial cells were swollen after 5 min of recirculation, and the changes grew markedly worse during 90 min of recirculation. Nuclear chromatin coarsened and mitochondria swelled up. Morphometry showed that the lumen narrowed as a result of endothelial swelling. In spite of variable degree of perivascular astrocytic edema, the outer capillary diameter was little changed in the experimental groups. It seems likely that endothelial swelling hampers postischemic circulation in incomplete ischemia accompanied by high lactic acidosis.

Acidosis↗
PubMed1983

Tissue lactic acidosis and ischemic brain damage.

Current evidence suggests that the brain has considerable potential to tolerate prolonged periods of complete ischemic anoxia. Moreover, the brain may be less damaged by complete ischemic anoxia than by severe incomplete ischemia. The accumulation of lactic acid in the brain during severe incomplete ischemia approaches three times the levels seen with complete ischemic anoxia, and this phenomenon is implicated in exacerbated biochemical and structural injury.

Acidosis↗
PubMed1983

Temporary clipping during early operation for ruptured aneurysm: preliminary report.

Temporary arterial occlusion was performed in 16 patients undergoing early aneurysm operation. Ten patients had a ruptured middle cerebral artery (MCA) aneurysm, and 6 had a ruptured anterior communicating artery aneurysm. Premature aneurysm rupture during operation necessitated temporary arterial occlusion in 10 patients. In 5 patients, temporary arterial occlusion was performed to facilitate dissection of the aneurysm. In 1 patient with a large MCA aneurysm, temporary occlusion was performed to provoke collapse of the completely exposed aneurysm sac, thus making clipping of the base possible. The results do not indicate that temporary occlusion by the standard aneurysm clips now in general use leads to angiographically detectable arterial wall changes or increased thromboembolic complications. Temporary clipping of the MCA proximal to the perforating arteries may be well tolerated for up to 20 minutes during early aneurysm operation. Temporary occlusion of one or both anterior cerebral arteries or temporary pericallosal clipping need not unconditionally lead to disastrous consequences if rendered necessary during aneurysm operations performed in the acute stage.

Adult↗
PubMed1981

The role of lactic acidosis in the ischemic nerve cell injury.

Severe incomplete cerebral ischemia of 30 min duration with CBF below 5% of normal was induced in rats by clamping both carotids and lowering BP. One group of rats were fasting (f-rats), while the other was infused with glucose before induction of the ischemia (g-rats). In f-rats the lactate accumulating in the cerebral cortex was about 15 mumol . g-1, whereas in g-rats it rose to about 35 mumol . g-1. In f-rats considerable recovery of the energy state and electrical activity occurred during recirculation, whereas in g-rats the energy failure persisted with no electrical activity reappearing. In f-rats the structural alterations were of minor severity, but in g-rats extensive progressive tissue damage was seen. The data indicate that the degree of tissue lactic acidosis has pronounced effects on the development of irreversible ischemic nerve cells injury.

Animals↗
PubMed1981

Brain lactic acidosis and ischemic cell damage: 1. Biochemistry and neurophysiology.

This study explores the influence of severe lactic acidosis in the ischemic rat brain on postischemic recovery of the tissue energy state and neurophysiological parameters. Severe incomplete brain ischemia (cerebral blood flow below 5% of normal) was induced by bilateral carotid artery clamping combined with hypovolemic hypotension. We varied the production of lactate in the tissue by manipulating the blood glucose concentrations. A 30-min period of incomplete ischemia induced in food-deprived animals caused lactate to accumulate to 15-16 mumol g-1 in cortical tissue. Upon recirculation these animals showed: (1) a considerable recovery of the cortical energy state as evaluated from the tissue concentrations of phosphocreatine, ATP, ADP, and AMP; and (2) return of spontaneous electrocortical activity as well as of somatosensory evoked response (SER). In contrast, administration of glucose to food-deprived animals prior to ischemia caused an increase in tissue lactate concentration to about 35 mumol g-1. These animals did not recover energy balance in the tissue and neurophysiological functions did not return. In other experiments the production of lactate during 30 min of complete compression ischemia was increased from about 12 mumol g-1 (normoglycemic animals) to 20-30 mumol g-1 by preischemic hyperglycemia and, in separate animals, combined hypercapnia. The recovery of the cortical energy state upon recirculation was significantly poorer in hyperglycemic animals. It is concluded that a high degree of tissue lactic acidosis during brain ischemia impairs postischemic recovery and that different degrees of tissue lactic acidosis may explain why severe incomplete ischemia, in certain experimental models, is more deleterious than complete brain ischemia.

Acidosis↗