Contribution of endothelin-1 to disruption of blood-brain barrier permeability in dogs

We examined the effect of intracisternal application of endothelin-1 (ET-1) on the permeability of fluorescein into the cerebrospinal fluid (CSF) in beagle dogs in order to evaluate its role in disruption of blood-brain barrier (BBB) permeability seen in the subarachnoid hemorrhage animal model. Intracisternal application of their autologous blood for producing a canine two-hemorrhage model revealed an enhanced fluorescein permeability into the CSF together with the development of cerebral vasospasm. A single dose of ET-1 (40 pmol/animal) significantly increased penetration of fluorescein compared with that in normal dogs. Although its magnitude was much less than that in the two-hemorrhage model after the first administration of ET-1, the second challenge of the same dose of ET-1 with a 48-h interval produced marked disruption of BBB permeability similar to those in the animal model. Moreover, the ET-1-induced enhancement of fluorescein permeability into the CSF was completely prevented by intracisternal pretreatment with an endothelin ET(A)-receptor selective antagonist, S-0139 (0.03 mg/kg), as were the ET-1-induced cerebral vasoconstriction and behavioral changes as previously reported. Thus, we conclude that ET-1 acting on the adventitial site of brain in dogs contributes to the disruption of BBB permeability via endothelin ET(A)-receptor mediation.     

Rapid regulation of P-glycoprotein at the blood-brain barrier by endothelin-1

The ATP-driven xenobiotic transporter P-glycoprotein is a critical element of the blood-brain barrier. To study regulation of P-glycoprotein function, we measured specific transport [(3'-oxo-4-butenyl-4-methyl-threonine(1), (valine(2)) cyclosporin (PSC833)-sensitive] of the fluorescent cyclosporin A derivative [N-epsilon(4-nitrobenzofurazan-7-yl)-D-Lys(8)]-cyclosporin A (NBDL-CSA) into the lumens of isolated rat brain capillaries using confocal microscopy and quantitative image analysis. Luminal NBDL-CSA accumulation was rapidly and reversibly reduced in a concentration-dependent manner by 0.1 to 100 nM endothelin-1 (ET-1). In this concentration range, ET-1 did not affect junctional permeability. The ET(B) receptor agonist sarafotoxin 6c also reduced transport. An ET(B) receptor antagonist blocked effects of ET-1 and sarafotoxin 6c; an ET(A) receptor antagonist was without effect. Consistent with this, immunostaining and Western blotting showed expression of the ET(B) receptor in brain capillary membranes. NBDL-CSA transport was also reduced by sodium nitroprusside, a NO donor, and by phorbol ester, a protein kinase C (PKC) activator. Inhibition of NO synthase (NOS) or PKC abolished the ET-1 effects. Thus, ET-1, acting through an ET(B) receptor, NOS, and PKC rapidly and reversibly reduced transport mediated by P-glycoprotein at the blood-brain barrier.     

Seizure-induced changes in the permeability of the blood-brain barrier following administration of anticholinesterase drugs to rats

Powerful inhibitors of acetylcholinesterase (phospholine iodide, paraoxon, and Soman) were used either separately or in combination with an anesthetizing drug (nembutal), an acetylcholine antagonist (atropine sulfate), or a convulsive drug (metrazole) to study the resistance of the blood-brain barrier to their effects. On the basis of measurements of acetylcholinesterase inhibition in rat brain stem and corpus striatum, it was concluded that these anticholinesterase drugs increased the permeability of the blood-brain barrier, provided that seizures were manifested shortly after administration of these drugs. Rats that were treated prophylactically with either nembutal or atropine sulfate did not convulse and, consequently, damage to the blood-brain barrier integrity was reduced significantly, despite a high degree of acetylcholinesterase and butyrylcholinesterase inhibition. It is suggested that anticholinesterase drugs enhance brain AChE inhibition by inducing strong convulsions and, thereby, increase their own penetration through the blood-brain barrier. It does not appear likely that acetyl- or butyrylcholinesterase located in the walls of the brain capillaries is involved in maintenance of the blood-brain barrier.     

Role of AT1 receptors in permeability of the blood-brain barrier in diabetic hypertensive rats

The precise mechanisms of vascular diseases in patients with diabetic hypertensive are not clearly understood. There are evidences of alteration in permeability of blood-brain barrier (BBB) in diabetic hypertensive rats. This study sought to examine the effect of candesartan on the systolic blood pressure and the brain endothelial barrier function and antioxidant enzymes in rat brain. Five groups of eight male Sprague-Dawley rats include: control group (gpI), diabetic hypertensive group (gpII), diabetic hypertensive group treated with candesartan (gpIII), diabetic hypertensive rats with epinephrine (gpIV) and diabetic hypertensive rats with epinephrine treated with candesartan (gpV). Diabetes was induced by single injection of 55 mg kg(-1) streptozotocin (STZ) i.p. Blood glucose was measured, rats with blood glucose higher than 300 mg/dl were identified as diabetic. After induction of diabetes, rats received L-NAME (0.5 mg/ml in drinking water for 1 week) starting on the day 4 after STZ injection. Systolic blood pressure (SBP) was recorded two times, at day 0 (before starting L-NAME) and at day 7 (after L-NAME treatment). Also, body weight was measured two times, at initial time (before STZ injection) and terminal (at the last day in the experiment). On the day of acute experiment, rats were anesthetized with sodium pentobarbital (35 mg/kg, i.p.). The integrity of the BBB was investigated using Evans blue (EB) dye (4 ml/kg, 2%). Epinephrine was used (40 micro g/kg) to increase the permeability of the brain. After decapitation, first the brain was removed, next homogenized and then the content of EB dye in the brain was measured. Another five groups of rats manipulated with the same manner except EB dye injection. These second group to evaluate antioxidant enzymes, reduced glutathione (GSH), lipid peroxides and superoxide dismutase (SOD) in brain homogenate. This study indicates that, in diabetic hypertensive rats, epinephrine administration leads to increase in microvascular-EB-albumin efflux to brain. However, candesartan treatment significantly attenuates this permeability to brain tissue and significantly increased GSH and SOD activity, while level of lipid peroxides was decreased significantly. The finding supports that the use of candesartan may offer a good alternative in the treatment of diabetic hypertensive subjects because it has an action that might be mediated through an antioxidant effect and beneficial effects on vascular endothelial permeability as well.     

一氧化碳在肝硬化大鼠肝性脑病形成中的作用

目的研究肝硬化大鼠一氧化碳(CO)水平与血脑屏障通透性改变的关系。方法将SD大鼠分为四氯化碳(CCl4)肝硬化模型组及对照组两组,用联二亚硫酸盐还原法测定血浆CO的含量,用伊文思蓝法测定血脑屏障通透性,生理多导仪测定血压、心率等。结果与对照组相比,肝硬化组血浆的CO水平明显升高[(18.4±1.8)mol/Lvs(10.3±1.2)mol/L,t=7.5,P<0.01],而平均动脉压降低[(18.9±0.7)kPavs(15.9±0.7)kPat=5.83,P<0.01];血脑屏障通透性增加,脑内伊文思蓝含量肝硬化组明显高于对照组[(18.5±1.4)ng/mgvs(15.1±1.1)ng/mg,t=3.94,P<0.01]。在肝硬化组血浆CO水平与脑内伊文思蓝含量呈正相关(r=0.72,P<0.01)而与平均动脉压呈负相关(r=-0.67,P<0.05)。结论CO作为一种信使分子,不仅参与肝硬化大鼠低血压的发生,还与血脑屏障通透性增加有关,可能是肝硬化诱发肝性脑病的重要介质之一。     

Enhancement of blood-brain barrier permeability by sodium caprate.

We examined the effect of sodium caprate on the integrity of the tight junctions of brain capillary endothelial cells, using a modified in-situ brain perfusion technique. Model hydrophilic compounds used were [3H]mannitol, [14C]sucrose, [3H]PEG900, [3H]PEG4000, FITC-dextran 4000, FITC-dextran 20000 and FITC-dextran 70000. The brain distribution volume of [14C]sucrose was significantly increased by sodium caprate in a concentration-dependent manner. The effective minimum concentration was 10mM. Furthermore, the effects of sodium caprate on the distribution volumes of hydrophilic compounds, [3H]mannitol, [14C]sucrose, [3H]PEG900, [3H]PEG4000, FITC-dextran 4000, FITC-dextran 20000 and FITC-dextran 70000, showed a molecular weight dependence. A plot of apparent permeation clearance against diffusion coefficient values suggested that 20 mM sodium caprate induced pores so large that the above compounds could pass through the blood-brain barrier with negligible friction within the pore. Our results showed that intracarotid sodium caprate perfusion could enhance the permeation of hydrophilic compounds through the blood-brain barrier.     

Inhibition of blood-brain barrier permeability to DL-propranolol by serum from acute renal failure rats

The effect of uranyl nitrate-induced acute renal failure on the brain uptake of DL-propranolol was investigated in rats with a series of tissue-sampling single-carotid injection techniques. When the buffer solution was used as an injection solution, the brain uptake index (BUI), the extraction ratio (ET), and the blood-brain barrier (BBB) permeability-surface area product (PSapp) and PSu (corrected PSapp for the unbound fraction) in uremic rats were significantly lower than those in control rats. These parameters for DL-propranolol were decreased significantly in both control and uremic rats receiving injection of the uremic serum. The PSu values in both of the control and uremic rats injected with either control or uremic rat serum were significantly higher than those in rats injected with the buffer solution, suggesting the presence of a protein-mediated transport mechanism; that is, the conventional assumption that the fraction of the drug which is available for the uptake in vivo is equal to the unbound fraction as measured in vitro may not hold. In contrast, the brain extraction of D-[14C]glucose, [3H]inulin and [3H]water, which show no binding to serum protein, was not affected by the coinjection of either control or uremic rat serum. On the other hand, using either the ultrafiltrate from serum (control and uremic) or supernatant fraction from heat-treated serum (control and uremic) as the injection solution, no significant difference in the PSu value for DL-propranolol was observed between control and uremic serum. These results suggest that (1) the decrease in the PSu value for DL-propranolol in uremic rats may be attributed mainly to the presence of an endogenous inhibitory substance(s) for the brain uptake or to the decrease in the exchangeable fraction in vivo in the uremic serum; (2) the decrease in the PSu value for DL-propranolol may also be partly attributed to the change in the BBB permeability and/or surface area; (3) the inhibitor for the brain uptake may be characterized as a temperature-sensitive and nonfiltrable substance(s) at physiological pH; and (4) the ability of protein-mediated transport for DL-propranolol into brain was decreased in uremic rats.     

Lonomia obliqua caterpillar venom increases permeability of the blood-brain barrier in rats.

Human envenoming by caterpillars of the saturniid moth Lonomia obliqua in southern Brazil produces a mild local response (erythema, some edema, and pain) and systemic effects that include incoagulable blood, renal failure and in severe accidents intracerebral hemorrhage. In this work, we used light and electron microscopy to investigate the morphological alterations in the brain and blood-brain barrier of rats injected intravenously with venom from L. obliqua spicules (200 microg/kg). Five semi-purified fractions of venom (200 microg/kg each) were also assayed. Quantitative morphological and ultrastructural analyses were done 6, 18, 24 and 72 h after the i.v. injection of venom and its fractions. Light microscopy showed that 6h after envenoming there was cerebellar edema, which decreased by 72 h. Intracerebral hemorrhage occurred in only one rat 24h after the injection of venom. Blood-brain barrier (BBB) breakdown, assessed by transmission electron microscopy based on the passage of an extracellular tracer (lanthanum nitrate) between brain capillary endothelial cells, was observed in the cerebellum and hippocampus 18 h after venom injection. At this time, the cerebellum was more sensitive to the venom than the hippocampus, as shown by the greater number of leaky vessels. The number of capillaries showing breakdown was lower after 72 h than after 18 h. None of the semi-purified fractions significantly increased the number of leaky vessels. These results indicate that L. obliqua caterpillar venom has a deleterious action on the rat BBB. The lack of effect of the venom fractions when administered alone suggested that a synergistic action of venom components may be responsible for the damage seen in the central nervous system, but this was not confirmed when three combinations of the fractions were tested.     

Changes in the blood-brain barrier permeability and in the brain tissue trace element concentrations after single and repeated pentylenetetrazole-induced seizures in rats.

The behaviour of brain capillary endothelium to the passage of macromolecules in single and repeated seizures conditions and its relationship to the brain trace element concentrations are the main subject of this study. For this purpose, animals were treated with either single or repeated doses of pentylenetetrazole (PTZ). As a marker of blood-brain barrier (B-BB) permeability changes, Evans Blue (EB) dye was used. Seizure activity was observed and seizure patterns and convulsion times were recorded. PTZ treatment induced generalised tonic-clonic seizure in all animals, but seizures were found to be lasting longer in single seizure group than repeated seizures group. Seizures induced by single dose PTZ treatment resulted in bilateral EB leakage in the preoptic area, caudate nucleus, putamen, thalamus, hypothalamus, midbrain, and the superior colliculus. However, repeated PTZ-induced seizures led to EB leakage in the brains of only few number of rats, and it was confined to hypothalamus, caudate nucleus, cerebellum, thalamus, and pons. On the other hand, while the levels of copper (Cu) and iron (Fe) in brain tissue were found to be decreased significantly in the repeated seizures group when compared with the other groups, the levels of zinc (Zn) did not show any differences between groups. These results indicate that the regional B-BB opening markedly differs between single and repeated PTZ-induced seizures group and this difference may be due to PTZ tolerance and changes in cerebral endothelial structure.     

Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats

Lobeline inhibits [3H]nicotine binding to rat brain membranes and nicotine-induced [3H]dopamine release from superfused rat striatal slices, indicating that lobeline acts as a nicotinic receptor antagonist. To determine whether lobeline also inhibits the effects of nicotine in vivo, the present study assessed the effect of lobeline pretreatment on nicotine-induced hyperactivity and sensitization. For 12 consecutive days, rats were injected subcutaneously with lobeline (3 mg/kg) or saline, followed 10 min later by nicotine (0.3 mg/kg) or saline injection, and activity was monitored. To determine if lobeline inhibits induction of sensitization to nicotine, 1 or 28 days later, rats were pretreated with saline followed by nicotine or saline. Lobeline attenuated nicotine-induced hyperactivity when both drugs were administered repeatedly. Although an initial injection of lobeline produced hypoactivity, tolerance to this effect developed. Importantly, tolerance did not develop to the lobeline-induced attenuation of nicotine hyperactivity. Lobeline attenuated the induction of sensitization to nicotine 1 day, but not 28 days, after the cessation of lobeline treatment. These results demonstrate that systemic administration of lobeline attenuates the locomotor-activating effects of repeated nicotine injection and the sensitization to nicotine, consistent with lobeline inhibition of nicotinic receptors and/or neurotransmitter transporters.     

动脉内输注高渗性甘露醇改变大鼠血脑屏障对甲氨喋呤的通透性(英文)

目的:研究高渗性溶液开放血脑屏障能否提高甲氨喋呤在皮层内的含量及这一开放过程的时程变化。方法:1)大鼠颈内动脉注射甘露醇,10分钟后分别从股静脉及颈内动脉给予甲氨喋呤,1小时后测定脑皮层内浓度。2)大鼠颈内动脉注射甘露醇,分别在不同时间间隔给予甲氨喋呤,给药1小时后测定脑皮层内药物浓度及脑皮层密度。结果:给予甘露醇后,静注甲氨喋呤和颈内动脉注射甲氨喋呤可以使相应侧脑皮层内浓度分别提高2.54倍和3.41倍。此作用在给予甘露醇10分钟后达到最大,6小时后完全消失;同时并不伴随明显的皮层密度改变。结论:甘露醇可逆性地开放血脑屏障,提高甲氨喋呤在脑皮层内的浓度,同时不会造成明显的脑损伤。     

Sex-dependent changes in blood-brain barrier permeability in epileptic rats following acute hyperosmotic exposure.

Osmotic and ionic balance in the central nervous system is especially regulated by solutes and water transport across the blood-brain barrier. The aim of this study was to investigate the effect of systemic hyperosmolarity on the blood-brain barrier permeability in both sexes after experimentally induced seizures. Eight groups of rats were studied: Group I: female control; Group II: male control; Group III: hyperosmotic female; Group IV: hyperosmotic male; Group V: non-hyperosmotic female + seizure; Group VI: non-hyperosmotic male + seizure; Group VII: hyperosmotic female + seizure; Group VIII: hyperosmotic male + seizure. In female rats with pentylenetetrazol-induced seizures, the extravasation of Evans-blue was greater in the brains of hyperosmotic animals than that in normal rats (P < 0.02). However, in male rats, the extravasation of Evans-blue was similar in the brains of hyperosmotic male rats and normal rats after seizure. Our results concluded that hyperosmotic female rats were shown to have a large increase in blood-brain barrier permeability in comparison to hyperosmotic male rats after pentylenetetrazol-induced seizures.     

姜黄素对大鼠缺血性脑损伤炎症反应和血脑屏障通透性的影响

目的研究姜黄素对大鼠脑缺血/再灌注损伤炎症反应和血脑屏障通透性的作用,并进一步探讨其潜在的机制。方法利用线栓法制备大鼠脑缺血/再灌注损伤模型,随机分为对照组、模型组和姜黄素治疗组。检测大鼠神经功能损伤评分和脑梗死体积;通过检测脑组织髓过氧物酶的含量说明中性粒细胞浸润和炎症反应的程度;检测脑组织伊文思蓝的含量说明血脑屏障的破坏程度;ELISA检测脑组织肿瘤坏死因子-α(TNF-α)的含量;免疫印记法检测基质金属蛋白酶-9(MMP-9)的表达变化。结果姜黄素治疗组减轻神经功能损伤、脑梗死体积,并减轻中性粒细胞在脑组织的浸润程度、改善血脑屏障完整性。同时姜黄素还可以降低脑组织TNF-α的含量以及MMP-9的表达水平。结论姜黄素通过减轻炎症反应和血脑屏障破坏对大鼠脑缺血/再灌注损伤起脑保护作用。姜黄素的脑保护作用可能与其降低TNF-α含量和MMP-9的表达有关。     

Nanoparticle surface charges alter blood-brain barrier integrity and permeability

PURPOSE: The blood-brain barrier (BBB) presents both a physical and electrostatic barrier to limit brain permeation of therapeutics. Previous work has demonstrated that nanoparticles (NPs) overcome the physical barrier, but there is little known regarding the effect of NP surface charge on BBB function. Therefore, this work evaluated: (1) effect of neutral, anionic and cationic charged NPs on BBB integrity and (2) NP brain permeability. Methods: Emulsifying wax NPs were prepared from warm oil-in-water microemulsion precursors using neutral, anionic or cationic surfactants to provide the corresponding NP surface charge. NPs were characterized by particle size and zeta potential. BBB integrity and NP brain permeability were evaluated by in situ rat brain perfusion. RESULTS: Neutral NPs and low concentrations of anionic NPs were found to have no effect on BBB integrity, whereas, high concentrations of anionic NPs and cationic NPs disrupted the BBB. The brain uptake rates of anionic NPs at lower concentrations were superior to neutral or cationic formulations at the same concentrations. CONCLUSIONS: (1) Neutral NPs and low concentration anionic NPs can be utilized as colloidal drug carriers to brain, (2) cationic NPs have an immediate toxic effect at the BBB and (3) NP surface charges must be considered for toxicity and brain distribution profiles.     

Permeability changes in the blood-brain barrier induced by nortriptyline and chlorpromazine

Intracarotid injections of nortriptyline and chlorpromazine evoked striking changes in the permeability of the blood-brain barrier of barbiturate-anesthetized rats. Alterations in permeability were dose-dependent, the threshold being between 5 and 10 μmol. Quantities 4 times threshold elicited 30-fold increases in the brain uptake of [¹⁴C]dopamine. From the LD50 values, it appears that the concentrations of nortriptyline and chlorpromazine which produced barrier changes were in the toxic range. The penetrabilities of [¹⁴C]d-mannitol and [¹⁴C]inulin were similarly enhanced by the drugs. The maximum uptake of mannitol was about twice that of inulin, indicating that barrier penetration may depend partially on molecular weight. This factor, in addition to the nonspecificity of uptake, suggests that the labeled compounds traversed the brain barrier by a drug-induced free-diffusion mechanism. Formation of micellar aggregates has been proposed as a causative factor in membrane lysis at the ultrastructural level; the effects of the pharmacologic agents on barrier permeability described in this study were correlated with the extent to which these compounds formed aggregates in aqueous solutions. Thus, the marked permeability changes might be related to disruptive effects of aggregates on brain endothelial membranes.     

Histamine- and acetylcholine-induced changes in the permeability of the blood-brain barrier of normotensive and spontaneously hypertensive rats

Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats were given saline, histamine (1.25, 2.5 or 5.0 micrograms/kg) or acetylcholine (1.0 or 2.0 micrograms/kg). Both agents caused a dose-dependent decrease in blood pressure which was greater in the spontaneously hypertensive animals. The permeability of the blood brain-barrier was measured with 131I-labelled serum albumin (RISA) or with 99mTc-sodium pertechnetate (TcO4-). The lowest dose of histamine caused a decrease in permeability of the blood-brain barrier to serum albumin in normotensive rats and acetylcholine caused an increase. Only the largest dose of histamine increased the permeability of the blood-brain barrier to serum albumin in spontaneously hypertensive rats. All doses of histamine and acetylcholine increased the permeability of the blood-brain barrier to sodium per technetate in nomotensive rats and the two lower doses of histamine increased the permeability in spontaneously hypertensive animals. This provides another example of the dissociation of change in the systemic blood pressure and change in the permeability of the blood-brain barrier.     

Transport of prostaglandin E1 across the blood-brain barrier in rats

The transport of prostaglandin E(1) (PGE(1)) across the blood-brain barrier (BBB) was characterized using an in-situ rat brain perfusion technique. The uptake of [(3)H]PGE(1) was not affected by shortchain monocarboxylic acids (butyric acid and valeric acid). On the other hand, uptake of [(3)H]PGE(1) was significantly inhibited by medium-chain monocarboxylic acids such as hexanoic acid, enanthic acid and octanoic acid. These medium-chain monocarboxylic acids showed a more potent inhibitory effect on [(3)H]PGE(1) uptake with increasing number of carbon atoms. In contrast, there was no decrease in [(3)H]PGE(1) transport by any dicarboxylic acids with 5-8 carbon atoms. Valproic acid decreased [(3)H]PGE(1) uptake, whereas p-aminohippuric acid, a substrate for the organic anion transporter family, did not inhibit [(3)H]PGE(1) transport. Bromocresol green, an inhibitor of prostaglandin transporter (PGT), strongly decreased [(3)H]PGE(1) transport across the BBB. In addition, digoxin and taurocholate, substrates for organic anion transporting polypeptide subtype 2 (Oatp2), significantly inhibited [(3)H]PGE(1) uptake. RT-PCR analysis revealed that PGT mRNA and Oatp2 mRNA are expressed in a capillary-rich fraction from rat brain. Thus, it is suggested that PGE(1) transport across the BBB is mediated by some specific transport systems, possibly by the members of the Oatp family.     

Modifications of the permeability of the blood-brain barrier and local cerebral metabolism in pentobarbital- and ketamine-anaesthetized rats

The state of deep surgical anaesthesia, induced by intraperitoneal injection of pentobarbital sodium (54 mg/kg) or ketamine hydrochloride (150 mg/kg) in the rat, was accompanied by a significant reduction in the permeability of the blood-brain barrier evaluated by calculating a unidirectional blood-to-brain constant (Ki) for the circulating tracer [14C]alpha-aminoisobutyric acid. Pentobarbital-induced anaesthesia was also characterized by a widespread and marked depression of local cerebral glucose utilization; on the contrary, when rats were anaesthetized with ketamine, cerebral glucose utilization increased in the striatum and hippocampus and decreased in the cerebellum and brain-stem. It is suggested, as a hypothesis, that two different mechanisms, depending on the kind of the anaesthetic drug used, may be involved in the changes in the permeability of the blood-brain barrier, observed in anaesthetized animals: (a) a neurogenic component; (b) a direct interaction of the anaesthetic with elements of the microvasculature.     

Ethanol enhancement of blood-brain barrier permeability to catecholamines in chicks

The effect of ethanol (EtOH) on permeability of the blood-brain barrier (BBB) to parenteral catecholamines was investigated in neonate chicks. Animals simulataneously administered EtOH, 2 g/kg, and norepinephrine (NE), 5 mg/kg, or epinephrine (E), 5 mg/kg, entered a roosting state which was more pronounced than that observed after either amine alone. Roosting chicks were killed 2 min after NE + EtOH and 10 min after E + EtOH for whole brain amine analysis. NE + EtOH treatment resulted in a 220% increase in whole brain NE over controls receiving this amine alone, whereas E + EtOH produced a 29% increase in brain E. EtOH alone did not alter endogenous levels of either amine in brain. Results indicate that EtOH, a solvent whose solubility characteristics allow it to penetrate easily both aqueous and lipoid membrane components, facilitates entry of E and NE into the brain of the neonate chick across an imperfect BBB present at hatching.     

Effect of alcohols on the permeability of blood-brain barrier

Effect of alcohols on the permeability of blood-brain barrier was studied in anaesthetised dogs using sodium fluorescein as circulant. Entry of sodium fluorescein in the cerebrospinal fluid (CSF) was measured spectrophotofluorometrically. Methyl, ethyl, propyl and butyl alcohols were used in the study. Methyl alcohol did not increase the entry of sodium fluorescein in CSF compared to control. However, ethyl, propyl and butyl alcohols significantly increased the entry of sodium fluorescein. The increase was dependent upon the length of alkyl chain of alcohols. Longer was the aliphatic chain more marked was the effect. The increase in permeability was also dependent upon the concentration of the alcohol. Thus 90% ethyl alcohol was more effective than 30% and this effect was concentration-dependent. The increase in permeability of blood-brain barrier could be correlated to the lipid solubility of alcohols.