Search

Background and Purpose: Clinical and experimental data indicate that hyperglycemia can aggravate the consequences of stroke and cerebral ischemia. The purpose of this study was to examine the effects of moderate hyperglycemia on the response of the blood-brain barrier to normothermic (37 degrees C) and hypothermic (30 degrees C) global forebrain ischemia., Methods: Sixteen rats underwent 20 minutes of four-vessel occlusion followed by 30 minutes of postischemic recirculation. We used the protein tracer horseradish peroxidase as an indicator of increased vascular permeability, and rats were perfusion-fixed for microscopic analysis. To produce moderate hyperglycemia, we gave an intraperitoneal injection of 50% dextrose 15 minutes before the ischemic insult., Results: After normothermic brain ischemia, normoglycemic rats (plasma glucose level, 115 +/- 3 mg/dl) demonstrated extravasated horseradish peroxidase mainly restricted to the cerebral cortex. In contrast, more severe and widespread protein extravasation was documented throughout the neuraxis of hyperglycemic (plasma glucose level, 342 +/- 27) rats. Sites of protein leakage included the cerebral cortex, striatum, hippocampus, thalamus, and cerebellum. Foci of protein extravasation were associated with pial and large penetrating vessels. Intraischemic hypothermia significantly attenuated the blood-brain barrier consequences of hyperglycemic brain ischemia., Conclusions: Under normothermic ischemic conditions, hyperglycemia significantly worsens the degree of acute blood-brain barrier breakdown compared with normoglycemia. Postischemic blood-brain barrier disruption may play an important role in the pathogenesis of increased brain damage associated with systemic hyperglycemia.

This study documents the ultrastructural features of acute neuronal injury following N-methyl-D-aspartate (NMDA) receptor activation. NMDA (100 nmol/microliters) or vehicle was infused over a 15-min period into the lateral ventricle of adult rats. After perfusion fixation, specimens demonstrating normal and abnormal patterns of vascular permeability to horseradish peroxidase were sampled for ultrastructural analysis. In NMDA-infused rats, brain regions exhibiting protein extravasation contained swollen dendritic profiles and abnormal neuronal perikarya. Although periventricular regions were most severely affected, parenchymal abnormalities were also detected in the cerebral cortex, septum, striatum, thalamus, hypothalamus and cerebellum. Mildly affected dendrites contained dark compact mitochondria, while in severely swollen dendrites mitochondria were enlarged with ruptured cristae. Focal sites of plasma membrane disruption were also detected within swollen dendrites. Swollen neurons commonly displayed peripheral pallor and increased numbers of cytoplasmic vacuoles. Other neurons appeared dark and shrunken, some containing disrupted mitochondria and pyknotic nuclei. Pretreatment with the NMDA antagonist MK-801 (2 mg/kg) attenuated the neuronal and dendritic alterations. In conditions where cerebrospinal fluid levels of glutamate are abnormally elevated, excessive NMDA receptor activation may lead to early vascular and neuronal complications which could work in concert to promote brain injury.

The purpose of this study was to document the early cerebrovascular consequences of excessive N-methyl-D-aspartate (NMDA) receptor activation. Five microliters of NMDA (100 nmol/microliters) or vehicle was infused over a 15-min period into the lateral ventricle of adult rats. The protein tracer horseradish peroxidase (HRP) was injected intravenously for blood-brain barrier (BBB) studies. The intraventricular infusion of vehicle (n = 5) caused no alterations in arterial blood pressure or microvascular damage away from the intraventricular probe tract. In contrast, NMDA infusion (n = 8) led to a gradual increase in arterial blood pressure (mean 36 mm Hg). Multifocal regions of HRP extravasation were observed bilaterally throughout the neuraxis following NMDA infusion. Sites of BBB disruption and hemorrhage included brain regions bordering ventricular spaces. In addition, isolated foci of protein extravasation were commonly detected in the cerebral cortex, thalamus, basal forebrain, septum and cerebellum. Pretreatment with the noncompetitive NMDA antagonist MK-801 (2 mg/kg) substantially reduced the BBB responses to NMDA. However, microvascular abnormalities were seen in NMDA-infused rats where blood pressure elevations were inhibited by blood removal. In addition to neurons, cerebral blood vessels are also acutely affected by NMDA receptor activation. Blockage of NMDA receptor channels following brain injury may potentially provide protection by attenuating BBB breakdown and subsequent brain edema.

The present studies were undertaken to examine 1) whether d-amphetamine sulfate administered to rats well after thrombotic infarction of the vibrissal cortical barrel-field within the primary somatosensory cortex affected the rate and completeness of behavioral recovery and 2) whether a dose-response relation exists between d-amphetamine sulfate dose and recovery of function. In a learning task requiring sensory-motor integration, 41 rats were trained to perform a motor response in a T-maze consequent to the detection of a vibrissal deflection cue. Once training was complete, unilateral (n = 29) or sham (n = 12) infarction was produced by a noninvasive photochemical technique. After infarction, T-maze performance was assessed repeatedly in rats receiving 2 (n = 10) or 4 (n = 10) mg/kg d-amphetamine sulfate or saline (n = 9) 24 hours prior to testing on days 4, 6, 9, and 11. The sham-operated control rats received d-amphetamine sulfate (n = 7) or no injections (n = 5). All three infarcted groups displayed a reliable and sustained behavioral deficit in performance that was not present in the sham-operated control animals. Although the performance of each infarcted group improved over the testing sessions after the first injection, the amphetamine-treated groups improved at a faster rate than the saline-injected group. The results further demonstrated a dose-response effect, with the 4 mg/kg amphetamine group recovering to within preinfarction levels 6-8 days earlier than the 2 mg/kg amphetamine and saline-injected groups. Moreover, both amphetamine-treated groups recovered more completely than the saline-injected group. Quantification of the chronic infarct area revealed no differences among the amphetamine-treated and saline-injected groups. These data provide further evidence of the facilitatory effect of d-amphetamine sulfate on recovery from brain injury and extend this effect to the enhancement of recovery subsequent to thrombotic infarction of the primary somatosensory cortex.

The consequences of acute amphetamine administration on the metabolic responsiveness of the cerebral cortex to physiologic activation were studied in normal and infarcted rats. Treated rats received a 4 mg/kg intravenous injection of d-amphetamine 1 hour before unilateral vibrissae stimulation and 2-deoxyglucose study. In nontreated normal rats, metabolic activation was restricted to the major relay stations of the vibrissae-barrel circuit. In amphetamine-treated rats, stimulation-induced increased glucose utilization was widespread, including ipsilateral and contralateral cortical regions outside the barrel field circuit. For example, an 84% increase in glucose utilization above control was seen in cortical areas anterior to the barrel field region. Increased glucose utilization induced by stimulation was severely depressed in nontreated rats that had undergone infarction of the left cortical barrel field 2 weeks previously. Vibrissae stimulation failed to increase glucose utilization significantly in cortical areas remote from the infarct. In contrast, bilateral increases in glucose utilization were observed within cortical regions of treated infarcted rats. For example, a 50% increase in glucose utilization was detected in cortical areas bordering the infarct. Thus, in the normal and infarcted rat, amphetamine appears to promote alternate circuit activation--a pharmacologic property that may be advantageous for recovery after injury.

A sample of 1,752 bovine sera collected from 99 herds throughout the Tenth Region, Chile, from March 8 to November 20, 1982, was analyzed for bluetongue (BT) antibodies using the immunodiffusion (ID) test. The prevalence of BT virus (BTV) antibody was 19.6%. Sixty-four (64.6%) herds showed at least 1 positive animal, which suggests an important antibody distribution in the area. The examination of 500 sera of sheep in 14 herds indicated the following results: 8/500 animals were positive in 5/14 of the herds.

Regional cerebral blood flow (rCBF) was studied autoradiographically in a murine model of focal epidural brain compression, and the effect of vitamin E administration was investigated. Mean cortical CBF was reduced to 0.48 to 0.50 ml/gm/min following 2 or 24 hours of compression. Early (2 hours) following subsequent decompression, a mixed pattern of hypoperfusion and hyperperfusion was observed. Twenty-four hours later, rCBF heterogeneities were less marked. Comparisons among animal groups raised on vitamin E-supplemented, vitamin E-normal, and vitamin E-deficient diets 2 hours after decompression revealed marked reductions in rCBF in the previously compressed cortex of the last two groups and hyperemia of the underlying hippocampus. The vitamin E-supplemented rats showed increased flow in the previously compressed cortex. In addition, vitamin E supplementation tended to eliminate rCBF gradients between subjacent zones. These data may help explain our previous observations of the beneficial effects of vitamin E on compression-induced brain edema.

The ability of neutral red to serve as an internal pH indicator in biological systems was tested in the rat brain after parenteral adminstration of the dye. The injected dye is avidly taken up by the brain cells and is distributed mainly in intracellular organelles. The ratio of optical signals recorded from the frozen brain at 445 and 530 nm and compared with calibration curves provides pH values. Color transition of neutral red ranges from 6.0 to 8.0 pH units. Topographic application of this method is particularly useful in studying local pH changes in brains with developing ischemic foci.

Phosphorus nuclear magnetic resonance with surface coils was used to investigate the regional metabolism of the rat brain in vivo under conditions of normoxia, severe hypoxemia, partial necrosis, and partial ischemia. The results show an increase in sugar phosphate and/or inorganic phosphate with injury in accordance with in vivo assays. The technique provides a powerful means of monitoring the metabolism of stroke and its response to therapy in vivo.

The layering of a luciferin-luciferase solution on brain slices makes endogenous ATP visible. Rat brains, frozen in situ and sliced at 16 micrometer thickness at a temperature of--15 degrees C, were fixed by a ternary mixture of ethanol, formalin and dioxane at--20 degrees C for 15 min, and dried at 40 degrees C for 12 h. Luciferin, luciferase and a small quantity of magnesium sulfate were dissolved into an arsenate buffer solution containing 1% polyvinylpyrrolidone, 2% gelatin and 1% glycerol. The solution was then frozen into a column, sliced at 40 micrometer thickness at--15 degrees C and placed on the precooled brain slice. A luminiferous luciferin-ATP reaction begins when the brain slice reaches room temperature and persists for more than 10 min. This technique therefore makes possible the optical and/or photographic determination of the endogenous concentration of brain ATP. Capability of the technique is also demonstrated.

Fine needle aspiration of lymph nodes was performed in 50 leprosy patients and was compared with usual techniques of bacillary smears taken from nasal mucosa, ear lobule and cutaneous lesion we found that the former was more sensible (30%) regarding bacteriologic and morphologic (34%) indices; moreover this proceeding was more sensible (50%) en patients with type II leprosy reaction. After 6 month-multi-therapy schedule in 3 patients, the morphologic index decreases 2 points (SFG) and bacteriologic index 1 + (mean value). It is concluded that fine needle aspiration of lymph nodes is a useful method, because of its simplicity and low traumatic effects and its sensibility to follow-up treatment and reactional phases.