The effect of intraventricular albumin in experimental brain oedema

Summary Therapy for vasogenic brain oedema (VBE) is still an unsolved problem. Experimental work with the aim of establishing an oncotherapeutic option is presented.VBE is performed by focal freeze injury in rats. Using a stereotactic head holder hypo- or hyperosmolar human serum albumin is administered via the intraventricular route. The goal is to enhance the migration of oedema fluid with the aid of oncotic pressures. Early and late results are obtained for each group respectively four and twenty-four hours after the infliction of cold injury. The efficacy of therapy is evaluated by cerebrospinal fluid (CSF) osmolality, cerebral water content, tissue specific gravity, and blood-brain barrier (BBB) permeability. Posttherapeutic values for CSF osmolality are obtained by cisterna magna puncture.Hyperosmolar CSF after performance of cold injury (p < 0.05) is thought to be a result of fluid accumulation in the traumatized region partially from the intraventricular space. Posttherapeutic values after hyperosmolar albumin administration have revealed iso-osmolar CSF, increase in specific gravity (p < 0.001), and decrease in BBB permeability (p < 0.05). These results are in accordance with withdrawal of oedema fluid into the ventricles which can be interpreted as a positive therapeutic effect. Late results in hyperosmolar group have disclosed a hypo-iso-osmolar CSF, persistent increase in specific gravity, and no regression. These values have shown that hyperosmolar albumin administration does not interfere with CSF circulation. Early results of hypo-osmolar albumin application are discouraging.This preliminary work of a therapeutic trial on VBE may be a basis for future investigations with different dosages and time modalities.     

Cerebral physiological and biochemical changes during vasogenic brain oedema induced by intrathecal injection of bacterial lipopolysaccharides in piglets

Summary. Summary.   Background: The objective of the study was to evaluate biochemical and physiological changes in an experimental model of vasogenic brain oedema utilising techniques also used in routine neuro-intensive care.   Method: 32 piglets were randomised to control or experimental group. The latter received an intrathecal injection of lipopolysaccharide (LPS) from E.coli (LPS group). Intracranial pressure (ICP) and mean arterial pressure (MAP) were measured continuously. Intracerebral microdialysis was used for analysing interstitial levels of glucose, pyruvate, lactate, glutamate, glycerol and urea every 30 min. Repeated calculations of mean hemispheric CBF were performed utilising an extra-cranial scintillation detector and intracarotid injection of ¹³³Xe. Cerebral specific gravity was measured and the brains were fixed for histological examinations.   Findings: After LPS injection ICP increased reaching a plateau phase after 4–7 hours and CBF increased by 46%. Histological examination showed inflammation with pronounced extravasation of granulocytes. A significant decrease in brain specific gravity (p= 0.022) was obtained. LPS caused a significant decrease in cerebral interstitial concentration of glucose (p=0.0035), and significant increases in lactate concentration (p=0.002) and lactate/pyruvate ratio (p=0.0017). A small but significant increase in glutamate was obtained (p=0.0219). Glycerol did not change significantly.   Interpretation: Intrathecal LPS caused an inflammatory reaction with extravasation of granulocytes, increased blood-brain barrier permeability and cerebral oedema. Biochemical analyses indicate increased glycolysis but no signs of cell membrane degradation. Published online June 20, 2002     

Attenuation of cryogenic induced brain oedema by arginine vasopressin release inhibitor RU51599

Summary Centrally released arginine vasopressin (AVP) has been implicated in the regulation of the brain water content and is elevated in the cerebrospinal fluid of patients with ischaemic and traumatic brain injuries. The protective effect of RU51599, which is a selective kappa opioid agonist as an AVP release inhibitor, on brain oedema was examined. Male Wistar rats, weighing 300 to 400 g each, were used. The cortical cryogenic injury was produced by application of a previously prepared metal probe cooled with dry ice to the dura of the right patietal region. Animals were separated into three groups. Group 1: sham operated rats without lesion production. Group 2: saline-treated rats with lesion production. Group 3: RU51599-treated rats with lesion production. In Group 3, rats were treated with RU51599 (0.1–3 mg/kg) at 30 minutes before lesion production, 1 hour, 2 hours, and 4 hours after lesion production. After 6 hours, animals were decapitated and brain water contents were measured using the dry-wet weight method. The extent of blood brain barrier (BBB) disruption was determined by assessment of Evans blue uptake based on extraction from tissue using dimethylformamide. The primary injured infarcted area was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Sodium and potassium contents in serum and brain tissue were measured using atomic absorption spectrophotometry. The antagonism of naloxone against protective effects of RU51599 on cryogenic induced brain oedema and on antinociceptive effects in acetic-acid treated animals was examined. Statistical analysis was performed using Dunnett-test and U-test following Kruskal-Wallis test. RU 51599 significantly reduced the brain water contents on the injured side and the contralateral non-injured side (p<0.01) after 4 administration of 1 and 3 mg/kg. RU51599 neither significantly inhibited BBB disruption nor reduced the primary injured infarcted area. RU51559 significantly increased brain sodium and potassium contents in the injured brain and also increased serum sodium levels (p<0.01). Naloxone antagonized the anti-oedema effects and antinociceptive effects of RU51599. These findings indicate that the AVP release inhibitor, RU51599 posssibly mediated by opioid receptors, has a potential protective effect on cryogenic-induced brain oedema and that centrally released AVP plays an important role in the progression of vasogenic brain oedema.     

大鼠侧脑室注射细胞因子等对脑损伤的形态学研究

目的：探讨大鼠侧脑室注射细胞因子和高渗液等致病因素对脑组织的损害作用。方法：48只雄性SD大鼠分为6组：侧脑室内分别注射TNF—α、10％NaCl、胰脂肪酶、白色念珠菌悬液及大肠埃希菌悬液，注射0．9％NaCl作为对照；以光镜和电镜观察不同损害因素对大鼠脑组织的作用。结果：TNF—α、10％NaCl、胰脂肪酶、真菌及细菌悬液均可招致不同程度的脑神经元和胶质细胞的水肿、核固缩、脑软化、轴突髓鞘板层结构紊乱、髓鞘脱失等病理改变。结论：促炎细胞因子、高渗状态、胰脂肪酶以及真菌和细菌感染都是重症急性胰腺炎病程中导致脑组织髓鞘、神经元和胶质细胞等损伤的病理因素。     

Neuroprotective effects of nimodipine and MK-801 on acute infectious brain edema induced by injection of pertussis bacilli to neocortex of rats

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