Antioxidants attenuate microvascular changes in the early phase of experimental pneumococcal meningitis in rats.

BACKGROUND AND PURPOSE: We tested in a rat meningitis model 1) whether pneumococcal cell wall components are capable of producing changes in regional cerebral blood flow, brain water content, and intracranial pressure similar to those we have already observed after intracisternal inoculation of live pneumococci and 2) whether antioxidants would modulate these alterations in the early phase of meningitis. METHODS: Regional cerebral blood flow as measured by laser Doppler flowmetry and intracranial pressure were monitored continuously for 4 hours after intracisternal challenge. Brain edema formation was assessed by brain water content determinations. We investigated the following groups: rats challenged intracisternally with the whole intact pneumococcal cell wall (n = 7) or the pneumococcal cell wall hydrolyzed by the M1-muramidase (n = 7); rats injected intracisternally with phosphate-buffered saline (n = 6); rats pretreated intravenously with superoxide dismutase conjugated with polyethylene glycol (10,000 units/kg) and injected intracisternally with cell wall components (n = 5) or phosphate-buffered saline (n = 6); rats injected intracisternally with phosphate-buffered saline and pretreated intravenously with polyethylene glycol (10% solution, 1.2 ml/kg, n = 5) or continuously treated with intravenous free superoxide dismutase (22,000 units/kg per hour, n = 6); and rats continuously treated intravenously with deferoxamine mesylate (10 mg/kg per hour) and injected intracisternally with cell wall components (n = 6) or phosphate-buffered saline (n = 7). RESULTS: Both pneumococcal cell wall preparations produced a significant increase in regional cerebral blood flow, intracranial pressure, and brain water content. Conjugated superoxide dismutase as well as deferoxamine prevented the increase in intracranial pressure and brain water content. In addition, the increase in regional cerebral blood flow as observed in untreated, cell wall-challenged rats (baseline, 100%; 183.1 +/- 12.3% after 4 hours, mean +/- SEM) was significantly attenuated by administration of both conjugated superoxide dismutase (136.6 +/- 14.1%) and deferoxamine (149.8 +/- 8.2%) (p < 0.05). Polyethylene glycol-conjugated superoxide dismutase alone produced an increase in regional cerebral blood flow (125.6 +/- 8.7% after 4 hours). We found that polyethylene glycol per se accounts for this action. CONCLUSIONS: These data show that pneumococcal cell wall components containing teichoic acid produce changes in regional cerebral blood flow, intracranial pressure, and brain water content and that oxygen radicals contribute to these pathophysiological alterations in the early phase of experimental pneumococcal meningitis.     

Evaluation of cerebral autoregulation following diffuse brain injury in rats

Abstract

The normal cerebral circulation has the ability to maintain a stable cerebral blood flow over a wide range of cerebral perfusion p(essures and this is known as cerebral autoregulation. This autoregulation may be impaired in the injured brain. Closed head injury was induced in 28 Sprague-Dawley rats weighing 400-450 g. Four groups were studied: control group, head injured rat from meter height using 350 g, 400 g and 450 g respectively. CBF, volume velocity was monitored using laser-Doppler flowmetry together with monitoring of ICP and arterial blood pressure. Correlation to assess the relationship between CBF and CPP was done in each animal every hour. If correlation coefficient was> 0.85 and CPP was within normal range, loss of autoregulation was hypothesized. Chi square test, ANOVA test and unpaired Studen(s t-test were done and significant level of p < 0.05 was established. Mean CBF in injured rats was significantly lower than controls (p = 0.028) at the fifth hour. CBV was lower in the group of 450 g 1 m impact than in controls at 3 h (p = 0.04). Velocity in the group ofall injured rats, was significantly lower than in controls at 3 h (p = 0.032) and at 4 h (p = 0.027). Loss ofautoregulation was seen during first four hours after trauma in all groups of rats who sustained injury. Statistical significant difference (p = 0.041) in loss of autoregulation between injured and control animals was seen. No loss of autoregulation was observed in the control group. In conclusion CBF and CPP provide information about loss of autoregulation in diffuse brain injury. Decrease in CBF and increase of ICP is observed as a result ofloss of cerebral autoregulation. Knowledge of loss of autoregulation could give important information and help in the management of head injured patients. [Neural Res 1997; 19: 393-402]     

Is nitric oxide involved as a mediator of cerebrovascular changes in the early phase of experimental pneumococcal meningitis?

Abstract

Nitric oxide (NO) is a mediator of haemodynamic changes and cytotoxicity in in vivo models of inflammation such as endotoxaemic shock. The purpose of this study was to investigate whether NO may be involved in the increase of cerebral blood flow (CBF), intracranial pressure (ICP) and brain water content, known to occur in the early phase of pneumococcal meningitis. Rats injected intracisternally with live pneumococci were either untreated or received 5 mg kg^–1 i.v. N^G-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. Pretreatment with L-NAME prevented the increase in CBF, ICP and brain water content, as seen in untreated animals. CBF tended to return towards baseline when rats were treated with L-NAME 2 h after pneumococcal injection. Whereas none of the untreated and L-NAME-pretreated animals died during the 6 h observation period 3 out of 9 rats treated with L-NAME and 7 out of 9 rats with simultaneous i.v. injection of L-NAME and L-arginine died. Our results provide preliminary evidence that NO may be involved as a mediator of CBF changes and oedema formation in the early phase of pneumococcal meningitis in the rat. NO inhibition, however, may have detrimental effects of still unidentified cause, as indicated by the increased mortality in treated animals. Further studies with analysis of the causes of mortality, structurally different NO synthase inhibitors and direct evaluation of NO synthase induction are needed to further support this hypothesis. [Neurol Res 1994; 16: 108-112]     

Effects of elevated ICP on brain function: can the multiparametric monitoring system detect the 'Cushing Response'?

The 'Cushing Response' is a significant phenomenon associated with elevated ICP. The purpose of our study was to examine the effects of the intracranial hypertension level and duration on the cerebral tissue physiology, using a Multiprobe assembly (MPA). The parameters monitored simultaneously included ICP, CBF, mitochondrial NADH redox state, extracellular K+ and H+ levels, DC potential and ECoG, calculated CPP and blood pressure. Two groups of rats were used. In one group, ICP was elevated to 50-60 mmHg for 13-15 min and, in the second group, ICP was elevated to 20 mmHg for 30 min. The results show that ICP of 50-60 mmHg led to CPP reduction below the lower limits of autoregulation. However, ICP of 20 mmHg, even for a prolonged period of time is completely tolerated. Additionally, we found that the 'Cushing Response', developed in the moderate treatment (ICP = 20 mmHg) is beneficial, assuring high CBF levels under intracranial hypertension. Furthermore, CBF and CPP monitoring, apparently, are not sufficient for autoregulation assessment; more parameters are needed.     

Effects of elevated ICP on brain function: Can the multiparametric monitoring system detect the 'Cushing Response'?

Abstract

The 'Cushing Response' is a significant phenomenon associated with elevated ICP. The purpose of our study was to examine the effects of the intracranial hypertension level and duration on the cerebral tissue physiology, using a Multiprobe assembly (MPA). The parameters monitored simultaneously included ICP, CBF, mitochondrial NADH redox state, extracellular K⁺ and H⁺ levels, DC potential and ECoG, calculated CPP and blood pressure. Two groups of rats were used. In one group, ICP was elevated to 50–60 mmHg for 13–15 min and, in the second group, ICP was elevated to 20 mmHg for 30 min. The results show that ICP of 50–60 mmHg led to CPP reduction below the lower limits of autoregulation. However, ICP of 20 mmHg, even for a prolonged period of time is completely tolerated. Additionally, we found that the 'Cushing Response', developed in the moderate treatment (ICP = 20 mmHg) is beneficial, assuring high CBF levels under intracranial hypertension. Furthermore, CBF and CPP monitoring, apparently, are not sufficient for autoregulation assessment; more parameters are needed.     

Is the acetazolamide test valid for quantitative assessment of maximal cerebral autoregulatory vasodilation? An experimental study

BACKGROUND AND PURPOSE: The cerebral vasodilating effect of acetazolamide (ACZ) injection has been used as an index of the autoregulatory vasodilation (or cerebral perfusion reserve). The question of whether the ACZ test assesses the maximal autoregulatory vasodilating capacity is not definitely resolved. The effects of ACZ injection on this reserve at a dose producing maximal vasodilation have never been evaluated and may help to resolve this problem. METHODS: The effect of ACZ injection on cerebral blood flow (CBF) autoregulation was tested in anesthetized rats. A pilot experiment evaluated the dose-effect relationship of injected ACZ, cumulative doses (n=4, group 1), and independent bolus doses (n=6, group 2). CBF was estimated by laser-Doppler flowmetry, and cerebrovascular resistance (CVR) was calculated from mean arterial blood pressure (MABP) and from CBF (expressed as a percentage of baseline CBF). A bolus of ACZ of 21 mg/kg produced the maximal cerebral vasodilation that could be obtained by ACZ administration. In the main experiment, MABP was lowered from 110 to 20 mm Hg by stepwise bleeding in 3 groups of 6 animals treated 10 minutes before bleeding by injection of saline (group 3), 7 mg/kg ACZ (group 4), or 21 mg/kg ACZ (group 5). RESULTS: The CVR-MABP relationship was linear in all groups, indicating that CBF autoregulation was still effective after ACZ administration. CONCLUSIONS: These results indicate that maximal ACZ-induced cerebral vasodilation is not quantitatively equivalent to maximal autoregulatory vasodilating capacity in anesthetized rats.     

Experimental pneumococcal meningitis. Effects of neuraminidase and other pneumococcal constituents on cerebrospinal fluid in the intact dog.

The intracisternal administration of a Type I pneumococcus to mongrel dogs resulted in spinal fluid abnormalities and clinical course and outcome similar to those of meningitis in humans. In order to define the pathogenic role of pneumococcal neuraminidase and other pneumococcal extracts in experimental meningitis, the following preparations were derived from the same Type I pneumococcus: crude neuraminidase, partially purified neuraminidase, heat-inactivated crude neuraminidase, and heat-killed pneumococci. These preparations were administered intracisternally daily for 5 days to a series of mongrel dogs. These substances did not produce clinical morbity similar to that observed in infected animals, even though there was significant decrease in the NANA content of cortical brain subcellular structures in the neuraminidase-treated dogs. It was concluded that the substances investigated were not responsible for morbidity and mortality in experimental pneumococcal meningitis. Both heat-killed pneumococci and the crude neuraminidase preparation elicited significant alterations in spinal fluid glucose and protein concentrations which were similar to those recorded in infected animals; however these abnormalities were not associated with significant morbidity. It is proposed that spinal fluid glucose and protein abnormalities may not be directly linked to brain damage or dysfunction in this experimental model, or in man.     

Role of substantia innominata in cerebral blood flow autoregulation

Ascending projections from the substantia innominata (SI) may have an important role in the regulation of cerebral blood flow (CBF). However, several reports have suggested that unilateral lesion of the SI does not affect CBF autoregulation. On the other hand, it is also reported that several cortical and subcortical functions may be regulated not only by ipsilateral SI, but also by contralateral SI. Thus, the objective of this study is to test the hypothesis that bilateral lesions of the SI affect CBF autoregulation. Experiments were performed on anesthetized male Sprague-Dawley rats. Ibotenic acid or physiological saline was microinjected into bilateral SI. Rats were classified into four groups as follows: bilateral SI lesion rats (ibotenic acid was injected bilaterally), left or right SI lesion rats (ibotenic acid was injected into the unilateral SI and saline into the contralateral SI), and control rats (saline was injected bilaterally). Ten days after injection, CBF in the left frontal cortex was measured by laser-Doppler flowmetry during stepwise controlled hemorrhagic hypotension. In bilateral SI lesion rats, CBF was started to decrease significantly at 80 mm Hg (p<0.01). In the other three groups, CBF was well maintained until 50 mm Hg. Changes in CBF through stepwise hypotension in bilateral SI lesion rats were significantly different from the other groups (p<0.01). These results suggest that bilateral SI regulates cortical vasodilator mechanisms during hemorrhagic hypotension. Under unilateral SI lesion, some compensatory effects from the contralateral SI may maintain CBF autoregulation.     

实验性脑血管痉挛时一氧化氮与超氧化物歧化酶对脑血流的作用研究

目的 探讨一氧化氮（ＮＯ）、超氧化物歧化酶（ＳＯＤ）分别及联合使用对大鼠实验性蛛网膜下腔出血（ＳＡＨ）后脑血管痉挛（ＣＶＳ）时脑血流（ＣＢＦ）的作用。方法 将３０只大鼠随机分成５组（每组６只）。Ａ组：假手术＋盐水,Ｂ组：ＳＡＨ＋盐水;Ｃ组：ＳＡＨ＋ＳＯＤ;Ｄ组：ＳＡＨ＋ＮＯＣ１２;Ｅ组：ＳＡＨ＋ＳＯＤ、ＮＯＣ１２。模拟制成４８ｈ后,通过Ｌａｓｅ－Ｄｏｐｐｌｅｒ血液仪观察各种药物持续静脉注射１ｈ内Ｃ     

Bradykinin antagonist counteracts the acute effect of both angiotensin-converting enzyme inhibition and of angiotensin receptor blockade on the lower limit of autoregulation of cerebral blood flow

The lower limit of autoregulation of cerebral blood flow (CBF) can be modulated with both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB). The influence of bradykinin antagonism on ARB-induced changes was the subject of this study. CBF was measured in Sprague–Dawley rats with laser Doppler technique. The blood pressure was lowered by controlled bleeding. Six groups of rats were studied: a control group and five groups given drugs intravenously: an ACE inhibitor (enalaprilat), an ARB (candesartan), a bradykinin-2 receptor antagonist (Hoe 140), a combination of enalaprilat and Hoe 140, and a combination of candesartan and Hoe 140. In the control group, the lower limit of CBF autoregulation was 54±9 mm Hg (mean±s.d.), with enalaprilat it was 46±6, with candesartan 39±8, with Hoe 140 53±6, with enalaprilat/Hoe 140 52±6, and with candesartan/Hoe 140 50±7. Both enalaprilat and candesartan lowered the lower limit of autoregulation of CBF significantly. The bradykinin antagonist abolished not only the effect of the ACE inhibitor but surprisingly also the effect of the ARB on the lower limit of CBF autoregulation, the latter suggesting an effect on intravascular bradykinin.     

Effects of porta-systemic shunting and ammonia infusion on cerebral blood flow autoregulation in the rat

Background: Portacaval shunting of blood, hyperammonemia, and impaired cerebral blood flow (CBF) autoregulation are assumed to be involved in the development of high intracranial pressure (ICP) in liver failure. In this study, we determined whether CBF autoregulation is impaired by portacaval anastomosis and hyperammonemia. Methods: Four groups of pentobarbital-sedated and mechanically ventilated rats were investigated after construction of a portacaval anastomosis or following sham operation. Half of the rats received either infusion of ammonia (55 μmol/kg/minute) or saline for 180 minutes. Arterial pressure and ICP was monitored, and lower limit of CBF autoregulation was determined. Results: Lower limit of autoregulation was preserved in all four groups of studied animals; vehicle lower limits were 40±2.3, 40±2, 54±1, and 51±3 mmHg in sham-operated rats, sham rats receiving ammonia infusion, portacaval anastomosis-vehicle animals, and portacaval anastomosis-hyperammonemia animals, respectively. The lower limit of auto-regulation was higher in portacaval anastomosis rats (p=0.01) compared to the sham-operated rats. Hyperammonemia in portacaval anastomosis rats did not aggravate this. Conclusion: Portacaval anastomosis and hyperammonemia does not impair the lower limit of CBF autoregulation. However, shunting of portal blood to the systemic circulation shifts the lower limit of autoregulation to higher blood pressure values, making the brain more sensitive to episodes of arterial hypotension.     

Global ischemia in dogs: cerebrovascular CO2 reactivity and autoregulation.

One hypothesis on the pathogenesis of post-ischemic-anoxic encephalopathy is impaired cerebral perfusion or the no-reflow phenomenon. Therapies aimed at preventing the development of this phenomenon are increased cerebral perfusion pressure (CPP) and hyperventilation or hypercapnia. Using a dog model in which we have described the progressive development of post-ischemic (PI) cerebral hypoperfusion after 15 minutes of global ischemia induced by aortic and vena cavae clamping, our aims in this study were to determine during the PI cerebral hypoperfusion period: (1) cerebrovascular reactivity to CO2, and (2) cerebral blood (CBF) autoregulation. Post-ischemic cerebral hypoperfusion to about 50% of normal was not accompanied by raised intracranial pressure (ICP) but cerebrovascular CO2 reactivity was markedly attenuated while maintaining some kind of autoregulatory phenomenon. Cerebral uptake of oxygen was not significantly affected by changing PACO2 from 20 to 60 torr at constant CPP or by changing CPP from 64 to 104 torr at constant PaCO2. These results suggest that increasing both CPP and hypocapnia/hypercapnia would not significantly attenuate PI neurological deficit after global cerebral ischemia. However, in two dogs inadvertently hemodiluted in the PI period, increasing CPP from 50 to 200 torr increased CBF by 200%, suggesting that hemodilution plus increased CPP may be effective therapy for amelioration of post-ischemic-anoxic encephalopathy. The significance of our findings on cerebrovascular CO2 reactivity and autoregulation with respect to the mechanism of the no-reflow phenomenon is discussed.     

Experimental pneumococcal meningitis: Cerebrovascular alterations,brain edema,and meningeal inflammation are linked to the production of nitric oxide

We investigated whether treatment with the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA) and the free radical scavenger superoxide dismutase influences cerebral blood flow changes, brain edema, and cerebrospinal fluid pleocytosis in early experimental pneumococcal meningitis. Compared to untreated infected rats, superoxide dismutase given 3 hours after infection significantly attenuated the increase of brain water content, intracranial pressure, and cerebrospinal fluid white blood cell count, but did not modulate the increase in regional cerebral blood flow. N-Nitro-L-arginine treatment (5 mg/kg intravenously, followed by 5 mg/kg/hour) reversed the increase in regional cerebral blood flow; prevented an increase in brain water content, intracranial pressure, and cerebrospinal fluid nitrite concentrations; and reduced cerebrospinal fluid white blood cell count. With a closed cranial window preparation, N-nitro-L-arginine prevented pneumococci-induced dilatation of pial arterioles. When the effective dose was increased twofold, the effects of N-nitro-Lvarginine became more pronounced but resulted in the death of 4 of 5 rats, probably due to hemodynamic side effects. In primary cultures of rat cerebral endothelial cells, nitrite concentrations increased after pneumococcal stimulation, which could be prevented by NvnitrovLvarginine and cycloheximide. These data suggest that (a) nitric oxide accounts for regional cerebral blood flow changes and pial arteriolar dilatation in the early phase of experimental pneumococcal meningitis; (b) both superoxide radical and nitric oxide are involved as mediators of brain edema and meningeal inflammation; and (c) cerebral endothelial cells can be stimulated by pneumococci to release nitric oxide presumably via the inducible nitric oxide synthase.     

Nitric oxide synthase inhibition depresses the height of the cerebral blood flow-pressure autoregulation curve during moderate hypotension.

Variations in the height of the CBF response to hypotension have been described recently in normal animals. The authors evaluated the effects of nitric oxide synthase (NOS) inhibition on these variations in height using laser Doppler flowmetry in 42 anesthetized (halothane and N2O) male Sprague-Dawley rats prepared with a superfused closed cranial window. In four groups (time control, enantiomer control, NOS inhibition, and reinfusion control) exsanguination to MABPs from 100 to 40 mm Hg was used to produce autoregulatory curves. For each curve the lower limit of autoregulation (the MABP at the first decrease in CBF) was identified; the pattern of autoregulation was classified as "peak" (15% increase in %CBF), "classic" (plateau with a decrease at the lower limit of autoregulation), or "none" (15% decrease in %CBF); and the autoregulatory height as the %CBF at 70 mm Hg (%CBF(70)) was determined. NOS inhibition decreased %CBF(70) in the NOS inhibition group (P = 0.014), in the control (combined time and enantiomer control) group (P = 0.015), and in the reinfusion control group (P = 0.025). NOS inhibition via superfusion depressed the autoregulatory pattern (P = 0.02, McNemar test on changes in autoregulatory pattern) compared with control (P = 0.375). Analysis of covariance showed that changes induced by NOS inhibition in the parameters of autoregulatory height are not related to changes in the lower limit, but are strongly (P < 0.001) related to each other. NOS inhibition depressed the autoregulatory pattern, decreasing the seemingly paradoxical increase in CBF as blood pressure decreases. These results suggest that nitric oxide increases CBF near the lower limit and augments the hypotensive portion of the autoregulatory curve.     

Cerebral blood flow velocity and failure of autoregulation in neonates: their relation to outcome of birth asphyxia.

Using the continuous wave Doppler technique, we examined the pulsatility index (PI) of the anterior cerebral artery in 14 asphyxiated infants. We also measured the blood pressure (BP) and fontanel pressure (FP) and calculated the cerebral perfusion pressure (CPP). According to the neurological prognosis, we divided the 14 infants into two groups and studied correlation of each factor. In the good-prognosis group (n = 11), PIs are within normal limits. There is a negative correlation between BP, CPP and PI, suggesting that the autoregulation of cerebral blood flow has been lost. On the other hand, there is no significant correlation between BP, CPP and PI in the poor-prognosis group (n = 3). These infants are thought to have lost the autoregulation, but their cerebral blood flow is not pressure-passive. Not only BP but also brain edema, vasodilation, and possibly other factors may contribute to determine the cerebral blood flow. Concerning FP, no remarkable correlations are found between two groups. It is therefore very important to monitor the PI, BP, FP in asphyxiated infants even if the degree of asphyxia is mild.     

Cerebral blood flow autoregulation in experimental liver failure.

Patients with acute liver failure (ALF) display impairment of cerebral blood flow (CBF) autoregulation, which may contribute to the development of fatal intracranial hypertension, but the pathophysiological mechanism remains unclear. In this study, we examined whether loss of liver mass causes impairment of CBF autoregulation. Four rat models were chosen, each representing different aspects of ALF: galactosamine (GlN) intoxication represented liver necrosis, 90% hepatectomy (PHx90) represented reduction in liver mass, portacaval anastomosis (PCA) represented shunting of blood/toxins into the systemic circulation thus mimicking intrahepatic shunting in ALF, PCA+NH(3) provided information about the additional effects of hyperammonemia Rats were intubated and sedated with pentobarbital. We measured CBF with laser Doppler, intracranial pressure (ICP) was measured in the fossa posterior and registered with a pressure transducer, brain water was measured using the wet-to-dry method, and cerebral glutamine/glutamate was measured enzymatically. The CBF autoregulatory index in both the GlN and PHx90 groups differed significantly from the control group. Conversely, CBF autoregulation was intact in the PCA and PCA+NH(3) groups despite high arterial ammonia, high cerebral glutamine concentration, and increased CBF and ICP. Increased water content of the brainstem or cerebellum was not associated with defective CBF autoregulation. In conclusion, impairment of CBF autoregulation is not caused by brain edema/high ICP. Nor does portacaval shunting or hyperammonemia impair autoregulation. Rather, massive liver necrosis and reduced liver mass are associated with loss of CBF autoregulation.     

利用激光散斑成像技术观察尤瑞克林对脑梗死大鼠脑血流的影响

目的 利用激光散斑成像技术研究尤瑞克林对大鼠脑梗死后局部脑血流的影响.方法 成年雄性SD大鼠24只,线栓法制备大鼠永久性大脑中动脉梗死模型.激光散斑成像系统观测缺血半球皮质及大脑中动脉供血区血流,2,3,5-三苯基氯化四氮唑(TTC)染色法测定脑梗死体积,并进行神经功能评分.结果 皮质及大脑中动脉供血区血流在大剂量组第1天及第2天给药后均有明显改善,部分大脑皮质血管增粗,血流速度加快,小剂量组及生理盐水组无明显变化,脑缺血48 h后,大、小剂量尤瑞克林组及生理盐水组的梗死体积分别为10.14%±3.02%,25.99%±3.90%,27.10%±3.32%,大剂量组与生理盐水组比较差异有统计学意义(F=61.14,P<0.01),小剂量组与生理盐水组比较差异无统计学意义.缺血后4 h,大剂量组神经功能损伤明显改善,小剂量组及生理盐水组无明显改变,36 h各组间的神经功能评分差异无统计学意义.结论 尤瑞克林可以减少大鼠局灶性脑缺血后梗死体积,延缓神经功能损伤,其作用可能与促进侧支循环的开放,增加大脑皮质和缺血区血流有关.     

Effects of microbial invasion on cerebral hemodynamics and oxygenation monitored by near infrared spectroscopy in experimental Escherichia coli meningitis in the newborn piglet.

This study was carried out to elucidate the pathophysiologic mechanism of cerebral hyperemia observed during the early phase of bacterial meningitis. We tested the hypothesis that microbial invasion through the blood-brain barrier is responsible for cerebral vasodilation and hyperemia in meningitis. Escherichia coli was given either intravenously (i.v.) or intracisternally (i.c.) to closely mimic the primary or secondary bacterial invasion occurring in meningitis and newborn piglets were grouped according to their invasion results (+ or -); 12 in the i.v. (+) group, 14 in the i.v. (-) group, 13 in the i.c. (+) group, 15 in the i.c. (-) group. The results were compared with eight animals in the control group. Near infrared spectroscopy (NIRS) was employed to monitor changes in total hemoglobin (HbT), oxygenated hemoglobin (HbO), deoxygenated hemoglobin (Hb), deduced hemoglobin (HbD), and oxidized cytochrome aa3 (Cyt aa3). HbT, as an index of cerebral blood volume, increased progressively in both i.v. (+) and i.v. (-) groups and became significantly different from control and baseline values at 2 h. Hb significantly increased only in i.v. (+) group. HbD, as an index of cerebral blood flow, decreased significantly in i.v. (+), i.v.(-) and i.c. (-) groups and this change was mitigated in i.c. (+) group, HbO was reduced in i.c. (-) group and this decrease was attenuated in i.c. (+) group. Increased Cyt aa3 was observed in all experimental groups after bacterial inoculation. Changes in ICP, blood pressure, cerebral perfusion pressure, blood or CSF glucose or lactate, CSF TNF-alpha level, or CSF leukocytes number were not associated with changes in NIRS findings. These findings suggest that primary or secondary bacterial invasion across the blood-brain barrier is primarily responsible for cerebral vasodilation and hyperemia observed during the early phase of bacterial meningitis.     

Transcranial Doppler assessment of the lower cerebral autoregulatory threshold

Continuous transcranial Doppler ultrasonography of the middle cerebral artery (TCD-MCA) has been proposed as a method of identifying the lower cerebral autoregulatory threshold. This study investigated the relationship between continuous TCD-MCA and cerebral blood flow (CBF) in sheep. Arterial blood pressure, intracranial pressure, CBF and left TCD-MCA were measured in 12 anaesthetized and ventilated merino sheep. Cerebral perfusion pressure (CPP) was reduced by haemorrhagic hypotension. Measurements were recorded continuously and breakpoint thresholds calculated by an analysis of variance. The TCD-MCA systolic velocity breakpoint (50 +/- 1.5 mmHg) did not significantly differ from the lower limit of autoregulation, identified by the CBF breakpoint (50 +/- 1.8 mmHg). The TCD-MCA diastolic velocity breakpoint occurred at a significantly higher level of CPP (64 +/- 2 mmHg) (P < 0.01). The relationship between TCD-MCA flow velocity and CBF thresholds has been described. Early divergence of flow velocity may represent a compensatory mechanism to maintain CBF.     

Impairment of autoregulation following cortical venous occlusion in the rat

Recent experiments showed an upward shift of the lower limit of autoregulation (AR) following photochemical occlusion of cortical veins in the rat. The goal of the present study was to prove the hypothesis that occlusion of cortical veins will be associated with impairment of the upper limit of autoregulation as well. In n = 28 Wistar rats unilateral frontoparietal cranial windows were drilled for transdural assessment of regional cerebral blood flow (rCBF) by laser Doppler scanning. The animals were allotted to two groups: (1) Group A (n = 5), control group for determination of the upper limit of autoregulation with stepwise induced arterial hypertension by intravenous administration of the alpha adrenergic drug methoxamine under continuous monitoring of mean arterial blood pressure (MABP); (2) Group B (n = 23), in which two cortical veins were photochemically occluded with rose bengal dye and fiberoptic illumination upon baseline CBF measurement. This was followed by repeated rCBF measurements under AR testing. Loss of AR in control Group A with passive increase of rCBF occurred at MABP of 147.5 +/- 2.9 mmHg. In Group B venous occlusion was followed by an initial phase of reduced rCBF, and then by pressure passive increases, thereby indicating loss of AR. Statistically significant changes of rCBF when compared to baseline MABP occurred at MABPbaseline + 10% (112.7 +/- 6.6 mmHg). We conclude that AR is impaired upon cortical venous occlusion with the propensity for hyperperfusion injury at a lower level of MABP when compared with a control group. In the context with earlier findings this may lead to narrowing of the corridor for MABP management following intra-operative occlusion of large cortical veins.