Effects of hyperoxia, glycerol and ventricular drainage on ICP and CBF in patients with increased ICP due to CSF circulatory-absorbance disturbance

The effects of hyperoxia, glycerol and ventricular drainage on intracranial pressure (ICP) and cerebral blood flow (CBF) were studied in cases with cerebrospinal fluid (CSF) circulatory-absorbance disturbance due to subarachnoid hemorrhage (SAH) or intraventricular hematoma. Ventricular fluid pressure (VFP) was monitored through a controlled ventricular drainage (CVD) tube using a Statham P-50 pressure transducer. CBF was measured by the 10mCi133Xe intravenous injection method using a Valmet BI-1400 rCBF analyzer. ISI (initial slope index) was used for the CBF value. Studied cases were 19 SAH patients and 2 hypertensive intracerebral hematoma cases with intraventricular hematoma. Hyperoxia included hyperbaric oxygen (HBO), reduced ICP and CBF. During pure oxygen inhalation at atmospheric pressure (1ATA . O2), there was a tendency toward a relationship showing that the higher the resting state ICP, the lesser the likelihood of a CBF decrease. This may indicate that increased ICP impairs cerebral vascular reactivity to hyperoxia in relation to the degree of elevation. The effects of hyperoxia on ICP and CBF were temporary and they promptly returned to the resting state after cessation of oxygen inhalation. In some cases, there was a rebound phenomenon in ICP after HBO. Glycerol administration reduced ICP and increased CBF. There was no clear correlation between resting state ICP and CBF increase after glycerol administration. The effects of glycerol were also temporary. ICP control by opening CVD increased CBF. There was a correlation between the level of resting state ICP and the CBF increase after the opening of CVD. In cases with CSF circulatory-absorbance disturbance, elevated ICP reduced CBF and may further worsen the cerebral damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of proteins in CSF of lateral and IVth ventricles during early development of fetal sheep

This study examines the relationship between plasma proteins in blood and in CSF in the developing brain of sheep fetuses between 30 and 60 days gestation. Five proteins account for the very high concentration of protein in fetal CSF (over 1000 mg/100 mg/100 ml at 30 days): alpha-feto-protein, fetuin, albumin, alpha 1-antitrypsin and transferrin; the concentration of each protein is similar in lateral and IVth ventricular CSF at 30 days. By 40 days there is considerable decrease in protein concentration in lateral ventricular CSF. At this age in the IVth ventricle the overall total was unchanged, although there were changes in concentration of individual proteins. At 60 days the concentration of each protein in both compartments had fallen below that at 40 days; the marked concentration difference between lateral and IVth ventricular CSF was still present. Experiments using i.v. [125I]- or [3H] labeled plasma proteins in 30-40-day fetuses showed that very little protein penetrated into lateral ventricular CSF by 3-5 h after injection; in the same experiments [125I]albumin reached a CSF/plasma ratio of about 15% in the IVth ventricle (compared with 55% for the natural steady state). Autoradiographic studies carried out on material from the same animals did not give evidence for transfer of labeled protein across the choroid plexuses although any such penetration may have been below the threshold of the method. Other explanations for the high concentration of protein in CSF that were considered include penetration via cerebral vessels and synthesis of plasma proteins by choroid plexus epithelial cells or neurons within the brain.     

Developmental changes in cerebrospinal fluid pressure and resistance to absorption in rats

Cerebrospinal fluid (c.s.f.) pressure and resistance to absorption have been studied in exteriorized fetuses (18 to 21 days gestation) from pregnant rats anaesthetised with pentobarbitone and in similarly anaesthetised postnatal rats at 1, 5, 10 and 30 days after birth and in adults. The resting c.s.f. pressure was low in fetuses (17-21 mm H2O) and it rose to 26-27 mm H2O at 1 and 5 days after birth. By 10 days after birth the pressure was 34 mm H2O after which time there was no further change. The plateau pressure response to different infusion rates was linear, but only up to pressures around 7-fold higher than the resting c.s.f. pressure. Hence, resistance to absorption was calculated for plateau pressures up to 140 mm H2O in fetuses, to 200 mm H2O in 1- and 5-day rats and to 240 mm H2O for 10-day, 30-day and adult rats. Resistance to absorption was not significantly different for the two measurement sites (lateral ventricle and subarachnoid space) at any age studied, showing that fluid can move freely through the ventricular system in young rats. The resistance to absorption was low in the fetuses, 10.8 and 16.3 mm H2O min/microliters at 18-19 and 20-21 days gestation, respectively. There was a sharp increase in resistance to 39.2 mm H2O min/microliters at 1 day after birth and thereafter there was a decrease to 6.8 mm H2O min/microliters at 30 days and this was similar to adult values. This decrease in outflow resistance from the first day after birth may be related to the increase in c.s.f. pressure and secretion rate that occur after birth in the rat.     

Intracerebroventricular infusion but not bolus injection of vasopressin increases the cerebrospinal fluid pressure in awake rabbits

The effect of intracerebroventricular infusion or injection of arginine vasopressin (AVP) was examined in awake rabbits with permanent ventricular cannulae. Intracerebroventricular infusion of artificial cerebrospinal fluid (CSF) 43 microliters min-1 containing AVP concentrations exceeding 0.4 ng ml-1, equivalent to an AVP infusion rate of 17.2 pg min-1, caused a dose-dependent increase in intracranial pressure (ICP) of 3 to 5 mmHg after 30-50 min of AVP infusion. Intracerebroventricular bolus injection of equivalent doses of AVP did not provoke changes in ICP. At the end of the experiments cisternal CSF concentrations of AVP were higher after infusion of AVP than after injection of the same amount of AVP. The mean arterial blood pressure increased slightly in the group of animals infused with AVP at rates above 17.2 pg min-1. It is concluded that intracerebroventricular infusion of AVP increases ICP in awake rabbits but the mechanism responsible for the elevation of ICP remains speculative.     

The effects of hyperoxemia on cerebral blood flow in subarachnoid hemorrhage patients

The effects of oxygen inhalation at atmospheric pressure (1 ATA.O2) on CBF were studied in subarachnoid hemorrhage (SAH) patients due to ruptured intracranial aneurysms to prove the usefulness of the "O2 response" test for the evaluation of the cerebral vascular response. "O2 response" means the CBF (or ICP) decrease during hyperoxemia. CBF was measured by 10 m Ci 133Xe intravenous injection method using rCBF analyzer BI-1400 (Valmet). Two-compartmental analysis was used for the calculation of initial slope index (ISI). Studied cases were 53 postoperative SAH patients and 100 times examinations were done under the condition of Rest-1 ATA.O2. The incidence of global disturbance of the O2 response was 33% from day 0 to 3, 31% during day 4 to 7, 30% during day 8 to 14, and 23% at day 15 to 30. But, after day 31, there was no case which revealed an impaired O2 response. It was not possible to detect focal or hemispheric abnormalities of the O2 response because of the limitation of noninvasive two-dimensional CBF measurement method employed. The causes of O2 response abnormality, within a month after the onset, were increased ICP, hydrocephalus and diffuse brain damage. Multiple regression analysis proved that elevated PaO2 is the major factor in reducing CBF. CBF and ICP correlation study showed that the higher the Rest ICP, the fewer the CBF decreases during pure O2 inhalation. This may indicate that the increase in ICP in the acute stage changes the O2 response according to the level of increased ICP.(ABSTRACT TRUNCATED AT 250 WORDS)     

PET and CBF Studies of Chronic Hydrocephalus: A Contribution to Surgical Indication and Prognosis

The authors investigate whether measurement of cerebral blood flow (CBF) in chronic hydrocephalus is a reliable indicator in selecting patients to undergo ventriculoperitoneal shunting. Global and regional CBF is quantified (Kety-Schmidt one-compartment model) by positron emission tomography in 21 patients. CBF is determined following inJection of 15 0-H2O at three time points 1 week before, 7 days after, and 7 months after shunting. The neurological status of these patients is classified, and cerebrospinal fluid (CSF) dynamics (continuous intracranial pressure [ICP] monitoring and CSF infusion tests) were assessed prior to surgery. Preoperative global CBF values correlate well with clinical outcome. Patients with a significantly lower global CBF value show clinical improvement after 7 months, whereas patients with higher CBF values do not (mean, 33 vs. 45 ml/1 00 ml per minute; p < 0 05). In contrast to conventional methods, including long-term ICP measurement and CSF infusion tests, preoperative global CBF values are discriminating in terms of clinical outcome. Thus, measurement of CBF may be helpful in evaluating the ultimate utility of shunt therapy in chronic hydrocephalus.     

Accelerated progression of kaolin-induced hydrocephalus in aquaporin-4-deficient mice.

Hydrocephalus is caused by an imbalance in cerebrospinal fluid (CSF) production and absorption, resulting in excess ventricular fluid accumulation and neurologic impairment. Current therapy for hydrocephalus involves surgical diversion of excess ventricular fluid. The water-transporting protein aquaporin-4 (AQP4) is expressed at the brain-CSF and blood-brain barriers. Here, we provide evidence for AQP4-facilitated CSF absorption in hydrocephalus by a transparenchymal pathway into the cerebral vasculature. A mouse model of obstructive hydrocephalus was created by injecting kaolin (2.5 mg/mouse) into the cisterna magna. Intracranial pressure (ICP) was approximately 5 mm Hg and ventricular size <0.3 mm(3) in control mice. Lateral ventricle volume increased to 3.7+/-0.5 and 5.1+/-0.5 mm(3) in AQP4 null mice at 3 and 5 days after injection, respectively, significantly greater than 2.6+/-0.3 and 3.5+/-0.5 mm(3) in wildtype mice (P<0.005). The corresponding ICP was 22+/-2 mm Hg at 3 days in AQP4 null mice, significantly greater than 14+/-1 mm Hg in wildtype mice (P<0.005). Brain parenchymal water content increased by 2% to 3% by 3 days, corresponding to approximately 50 muL of fluid, indicating backflow of CSF from the ventricle into the parenchymal extracellular space. A multi-compartment model of hydrocephalus based on experimental data from wildtype mice accurately reproduced the greater severity of hydrocephalus in AQP4 null mice, and predicted a much reduced severity if AQP4 expression/function were increased. Our results indicate a significant role for AQP4-mediated transparenchymal CSF absorption in hydrocephalus and provide a rational basis for evaluation of AQP4 induction as a nonsurgical therapy for hydrocephalus.     

Histochemical changes in the rat spinal cord after exposure to 6-aminonicotinamide

Summary The histochemical localization and activity of 5 hydrolytic and 5 oxidative enzymes in the spinal cord, spinal ganglion and muscle of the adult rat were studied at intervals of 1, 2, 3 and 4 weeks after weekly intraperitoneal (i.p.) injections of 5 mg/kg of antimetabolitic 6-aminonicotinamide (6-AN) and also 24 h after an injection of 20 mg/kg 6-AN. The rats were decapitated. One part of the spinal cord was frozen with liquid nitrogen and one part fixed in formalin.Seven days after the injection of 5 mg/kg proliferation of the glia in the center of the anterior grey matter of the spinal cord occurred accompanied by marked ATPase and acid phosphatase activity. A loss of histochemical activity in oxidative enzymes, especially of glucose-6-phosphate dehydrogenase, occurred. After the 3rd and 4th doses of 5 mg/kg i.p. the histochemical activity increased, especially in the capillaries. After a 20 mg/kg dose of 6-AN a marked decrease in activity of the oxidative and hydrolytic enzymes in the grey and white matter of the spinal cord was noted.We observed selective gliosis in the intermediate zone of the anterior horn and in rats receiving several doses of 6-AN, we also observed morphological and histochemical compensation. Striated skeletal muscle remained unchanged.Abbrevietions AChE acetylcholinesterase - ATPase adenosine triphosphatase - Acid phase acid phosphatase - Alk. phase alkaline phosphatase - G6PD glucose-6-phosphate dehydrogenase - Nonspec. Est.ase unspecific esterase - NaD H₂ reduced NAD dehydrogenase - SDH succinate dehydrogenase - LDH lactate dehydrogenase - Ubiq. Ubiquinone     

Intracerebroventricular infusion but not bolus injection of vasopressin increases the cerebrospinal fluid pressure in awake rabbits

The effect of intracerebroventricular infusion or injection of arginine vasopressin (AVP) was examined in awake rabbits with permanent ventricular cannulae. Intracerebroventricular infusion of artificial cerebrospinal fluid (CSF) 43 μl min^–1 containing AVP concentrations exceeding 0.4 ng ml^–1, equivalent to an AVP infusion rate of 17.2 pg min^–1, caused a dose-dependent increase in intracranial pressure (ICP) of 3 to 5 mmHg after 30-50 min of AVP infusion. Intracerebroventricular bolus injection of equivalent doses of AVP did not provoke changes in ICP. At the end of the experiments cisternal CSF concentrations of AVP were higher after infusion of AVP than after injection of the same amount of AVP. The mean arterial blood pressure increased slightly in the group of animals infused with AVP at rates above 17.2 pg min^–1. It is concluded that intracerebroventricular infusion of AVP increases ICP in awake rabbits but the mechanism responsible for the elevation of ICP remains speculative.     

6-Aminonicotinamide-induced hydrocephalus in suckling mice

Following a single intraperitoneal injection of 6-aminonicotinamide (6-AN, 50 mg/kg of body weight) into newborn mice of the Institute of Cancer Research strain, hydrocephalus consistently developed nine days after injection, with rapid progression. All of these mice died before reaching adulthood. The most striking early histologic change in these mice was cytoplasmic vacuolation of ependymal cells, which was observed as early as 24 hours after injection. Vacuolation of subependymal astrocytes appeared during the next few days. After day seven, the aqueduct was obliterated by swollen vacuolated ependymal cells and subependymal astrocytes. The aqueduct remained obliterated even after the vacuolation of the ependymal cells subsided after day nine, when vacuolation of subependymal astrocytes was still pronounced. These morphological observations reveal that, in newborn mice, the ependymal cells are the most sensitive to the toxic action of 6-AN and suggest that the pathogenesis of 6-AN-induced hydrocephalus is likely to be due to the combination of ependymal cell damage and compression of the lumen by the edematous periaqueductal gray matter. This is a highly reproducible animal model of drug-induced hydrocephalus.     

Hypertonic fluid resuscitation from subarachnoid hemorrhage in rats: a comparison between small volume resuscitation and mannitol

OBJECTIVE: Death and severe morbidity after subarachnoid hemorrhage (SAH) are mainly caused by global cerebral ischemia through increased intracranial pressure (ICP) and decreased cerebral blood flow (CBF). We have recently demonstrated neuroprotective effects of small volume resuscitation (7.5% saline in combination with 6% dextran 70) in an animal model of SAH, leading to normalization of increased ICP, reduced morphological damage and improved neurological recovery. In the present study, we compared the concept of small volume resuscitation represented by two clinically licenced hypertonic-hyperoncotic saline solutions with the routinely used hyperosmotic agent-mannitol-and investigated their effects on ICP, CBF, neurological recovery and morphological damage after SAH in rats. METHODS: 60 dextran-resistant Wistar rats were subjected to SAH by an endovascular filament. ICP, MABP (mean arterial blood pressure) and bilateral local CBF were continuously recorded. All animals were randomly assigned to four groups: (I) NaCl 0.9% (4 ml/kg bw), (II) 7.5% NaCl+6% dextran 70 (4 ml/kg bw), (III) 7.2% NaCl+HES 200,000 (4 ml/kg bw) and (IV) 20% mannitol (9.33 ml/kg bw) given 30 min after SAH. Neurological deficits were assessed on days 1, 3 and 7 after SAH. The morphological damage was evaluated on day 7 after SAH. RESULTS: The induction of SAH resulted in an immediate ICP increase to 46.6+/-3.2 mm Hg (mean+/-S.E.M.) and 29.6+/-1.3 (mean+/-S.E.M.) mm Hg 90 min post-SAH. While a treatment with both hypertonic saline solutions (II, III) decreased ICP as well as the 20% mannitol solution, only the group treated with hypertonic saline and dextran 70 (II) showed an increase of ipsilateral CBF for 20 min after the infusion and significantly more surviving neurons in the motorcortex and caudoputamen. Mortality was reduced from 60% (I) and 73% (III and IV), respectively, to 40% in group II. CONCLUSION: Of all hypertonic solutions investigated, small volume resuscitation with NaCl 7.5% in combination with 6% dextran 70 evolved to be most effective in terms of reducing the initial harmful sequelae of SAH, leading to lowered ICP and less morphological damage after SAH in the rat.     

2058例重型颅脑创伤颅内压动态监护分析

目的 探讨颅内压(intraeranial pressure,ICP)持续动态监护对重型颅脑创伤(severe traumatic brain injury,sTBI)救治的指导意义.方法 分别采用脑窜内及脑实质内ICP监护法,对2058例sTBI患者进行ICP持续动态监护,观察ICP与患者生命体征、临床表现和预后的关系,分析其对脑室外引流及其他降颅压治疗的指导作用.结果 ICP持续动态监护末并发严重颅内感染及出血,脑室外引流对持续ICP增高者有显著的治疗作用,ICP值与患者预后呈显著负相关.结论 ICP持续动态临护安全、易行,其有助于sTBI患者病情变化的及时、正确判断,能为临床医生制定治疗方案及预后病人评估提供重要的参考依据.     

Developmental profile of plasma proteins in human fetal cerebrospinal fluid and blood

Total protein, alphafetoprotein, albumin, prealbumin, alpha-1-antitrypsin, transferrin and ceruloplasmin levels were measured in samples of human fetal and neonatal cerebrospinal fluid (CSF) (97 cases), obtained between 12 and 41 weeks of gestation. In 39 of these cases (13 to 40 weeks gestation) plasma was also available for comparative analysis. CSF was collected from lateral ventricles in the first half of gestation and from the lumbar region in the second. Since these CSF samples were obtained from different sites, the protein levels in the lateral ventricle (early) samples could not be compared directly with those in the lumbar (later) samples. However, the mean protein levels in the lumbar samples were lower than those in the ventricular samples, which is in accord with the decline in CSF protein levels described in maturing animal fetuses. Despite a wide scatter of results, particularly in the first half of gestation, significant decline in the level of CSF alphafetoprotein was demonstrated during both first and second halves of gestation, and of albumin and prealbumin in the second half. No sex differences were found except for ceruloplasmin in lumbar CSF later in gestation, when males had higher levels than females. In fetal plasma, protein levels increased with increasing gestation apart from alphafetoprotein and prealbumin which both declined progressively. CSF/plasma ratios were dissimilar for different proteins, and changed with increasing gestation. These findings support the concept that the human fetal blood brain barrier matures early.     

In vivo multiparametric monitoring of brain functions under intracranial hypertension following mannitol administration

OBJECTIVE: Over the last 20 years, mannitol has replaced other osmotic diuretics. Its beneficial effects on intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral blood flow (CBF) and brain metabolism are widely accepted. In the present study, we tested the effect of mannitol injection on brain hemodynamic, metabolic, ionic and electrical state in rats exposed to intracranial hypertension. METHODS: The parameters monitored simultaneously included ICP, CBF using the laser Doppler flowmetry, mitochondrial NADH redox state by the fluorometric technique, extracellular K(+) and H(+) levels, DC potential, ECoG, blood pressure and calculated CPP. ICP was elevated to 30 mmHg for 30 minutes and mannitol was injected 15 minutes post-ICP elevation. RESULTS: Our results showed that mannitol decreased ICP, and improved the levels of MAP, CPP and CBF. Moreover, mannitol completely prevented mortality following intracranial hypertension in rats. CONCLUSION: It seems that the multiparametric monitoring approach, used in intracranial hypertension models, is an important tool for brain functional state evaluation.     

Alpha-Stat Versus pH-Stat Guided Ventilation in Patients with Large Ischemic Stroke Treated by Hypothermia

Background  Moderate hypothermia (MH) is a therapeutic approach for ischemic stroke as well as cardiac arrest. Two different technical strategies of ventilation during MH called alpha- and pH-stat dramatically influence cerebral blood flow (CBF). In turn this might influence neuronal damage and intracranial pressure (ICP). Therefore, effects of ventilation on CBF and ICP were measured in patients undergoing MH because of large ischemic stroke to address optimal ventilation management. Methods  Eight patients (n = 8) with large ischemic stroke in the territory of the middle cerebral artery (MCA) were treated by MH of 33°C within 24 h after symptom onset. MH was applied at least for 72 h. Each day, patients were ventilated repetitively with either alpha-stat or pH-stat for 60 min periods. Alpha-stat was applied between the measurements. ICP, CBF, and mean arterial blood pressure (MABP) were measured. The xenon clearance method was used to assess CBF at the bedside. Results  There were no significant differences between ICP values for alpha-stat or pH-stat during days 1 and 2 after induction of hypothermia. However, ICP was higher in the pH- as compared to the alpha-stat group (P < 0.05) and exceeded a mean of 20 mmHg on day 3. pH-stat led to a significant increase of CBF in all measures (P < 0.05), while MABP was unaffected. Conclusions  pH-stat implies a better CBF to the injured brain, while it might be dangerous by elevating ICP in more subacute stages.     

Changes in cerebrospinal fluid pressure and outflow from the lateral ventricles during development of congenital hydrocephalus in the H-Tx rat

Rats from the H-Tx strain develop hydrocephalus at 19 or 21 days gestation, and were used to measure cerebrospinal fluid pressure and resistance to absorption at different ages between 19 days gestation and 21 days after birth. The results were compared with earlier experiments on normal rats from a different strain. The resting pressure of cerebrospinal fluid in the lateral ventricles of hydrocephalic rats was not elevated above normal up to 10 days after birth, but by 21 days the pressure was nearly twice that of normal rats. Resting pressure measured from the cisterna magna was not significantly different from lateral ventricle pressure. In hydrocephalic rats the resistance to outflow from the lateral ventricles measured by constant-rate infusion, was the same as for normal rats at 19 days gestation but subsequently increased to a value above normal at 1 day after birth. This high resistance was maintained throughout the postnatal period without the postnatal decline seen in normal rats. Resistance to absorption from the cisterna magna, on the other hand, was similar to that in normal rats of the same age. Thus the results of these experiments showed that in the H-Tx strain, cerebrospinal fluid pressure increased only in the late stages of hydrocephalus and that the condition is associated with a reduction in outflow from the ventricular system.     

Congenital hydrocephalus: A new experimental model with histopathological study

We describe a new experimental model of fetal hydrocephalus in the lamb. 14 sheep were operated on at 100–120 days gestation for the insertion of a catheter into the fetal aqueduct of Sylvius, to block cerebrospinal fluid (CSF) flow. After the operation the intracranial pressure (ICP) was measured daily from the distal end of the catheter. The progress of ventricular dilatation was recorded by ultrasound. At ICP 100 mm/H²O the animals were killed for postmortem examination of the fetuses. Neuropathological examination showed massive dilatation of the ventricles. The ependymal cells appeared to be flat and the cellular lining disrupted. Growth of pseudocysts, cellular stratification and proliferation of the paraventricular germinal cells were observed also. With our new experimental model we were able to control the rise in ICP and correlate the evolution of the anatomical damage with the duration of high ICP and with the gestational age at which it began. Our model can also be used at early stages of gestation for reversing the development of hydrocephalus. It might therefore provide information on the suitability of fetal hydrocephlus surgery.

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Sommario Gli AA. presentano un modello sperimentale di idrocefalo fetale ottenuto in pecore gravide al 100° giorno di gestazione, introducendo un catetere nell’acquedotto di Silvio. L’idrocefalo viene monitorizzato mediante ultrasuoni e la misurazione della pressione del liquido cerebrospinale. Gli animali vengono sacrificati quando la pressione intracranica raggiunge i 100 mm di H₂O. Lo studio neuropatologico, rispetto a casi di controllo a periodi di età gestazionale, evidenzia una marcata dilatazione dei ventricoli, un appiattimento dello strato cellulare ependimale, una proliferazione delle cellule germinali periventricolari, presenza di pseudorosette cellulari nella sostanza bianca subependimale.

     

Changes in cerebral blood flow during cerebrospinal fluid pressure manipulation in patients with normal pressure hydrocephalus: a methodological study.

The combination of cerebral blood flow measurement using (15)O-water positron emission tomography with magnetic resonance coregistration and CSF infusion studies was used to study the global and regional changes in CBF with changes in CSF pressure in 15 patients with normal pressure hydrocephalus. With increases in CSF pressure, there was a variable increase in arterial blood pressure between individuals and global CBF was reduced, including in the cerebellum. Regionally, mean CBF decreased in the thalamus and basal ganglia, as well as in white matter regions. These reductions in CBF were significantly correlated with changes in the CSF pressure and with proximity to the ventricles. A three-dimensional finite-element analysis was used to analyze the effects on ventricular size and the distribution of stress during infusion. To study regional cerebral autoregulation in patients with possible normal pressure hydrocephalus, a sensitive CBF technique is required that provides absolute, not relative normalized, values for regional CBF and an adequate change in cerebral perfusion pressure must be provoked.     

Chronic hydrocephalus-induced changes in cerebral blood flow: mediation through cardiac effects.

Decreased cerebral blood flow (CBF) in hydrocephalus is believed to be related to increased intracranial pressure (ICP), vascular compression as the result of enlarged ventricles, or impaired metabolic activity. Little attention has been given to the relationship between cardiac function and systemic blood flow in chronic hydrocephalus (CH). Using an experimental model of chronic obstructive hydrocephalus developed in our laboratory, we investigated the relationship between the duration and severity of hydrocephalus and cardiac output (CO), CBF, myocardial tissue perfusion (MTP), and peripheral blood flow (PBF). Blood flow measures were obtained using the microsphere injection method under controlled hemodynamic conditions in experimental CH (n=23) and surgical control (n=8) canines at baseline and at 2, 4, 8, 12, and 16 weeks. Cardiac output measures were made using the Swan-Ganz thermodilution method. Intracranial compliance (ICC) via cerebrospinal fluid (CSF) bolus removal and infusion, and oxygen delivery in CSF and prefrontal cortex (PFC) were also investigated. We observed an initial surgical effect relating to 30% CO reduction and approximately 50% decrease in CBF, MTP, and PBF in both groups 2 weeks postoperatively, which recovered in control animals but continued to decline further in CH animals at 16 weeks. Cerebral blood flow, which was positively correlated with CO (P=0.028), showed no significant relationship with either CSF volume or pressure. Decreased CBF correlated with oxygen deprivation in PFC (P=0.006). Cardiac output was inversely related with ventriculomegaly (P=0.019), but did not correlate with ICP. Decreased CO corresponded to increased ICC, as measured by CSF infusion (P=0.04). Our results suggest that CH may have more of an influence on CO and CBF in the chronic stage than in the early condition, which was dominated by surgical effect. The cause of this late deterioration of cardiac function in hydrocephalus is uncertain, but may reflect cardiac regulation secondary to physiologic response or brain injury. The relationship between cardiac function and CBF should be considered in the pathophysiology and clinical treatment of CH.     

INHERITED PRENATAL HYDROCEPHALUS IN THE H–Tx RAT: A MORPHOLOGICAL STUDY

The H-Tx rat has inherited hydrocephalus which is present at birth. In order to investigate the onset and early stages of hydrocephalus, the heads of fetuses from 16 to 21 days gestation and at 1 day after birth, were serially sectioned using conventional wax histology. Lateral and third ventricle volumes were measured with a graphics tablet and microcomputer. Hydrocephalus was first detected at 18-20 days gestation by enlarged lateral ventricles and it was sometimes accompanied by a large third ventricle. Most hydrocephalics had a non-patent cerebral aqueduct between the third ventricle and the posterior collicular recess and the remainder (about 25%) had an aqueduct which was patent but with a smaller lumen than in non-hydrocephalic littermates. Some fetuses prior to 18 days gestation with normal lateral ventricles also had non-patent aqueducts. Abnormal aqueducts were lined by ependymal cells which were ventrally displaced by thickening of the overlying midbrain; also the subcommissural organ was foreshortened. Infusion with fluorescent markers confirmed that the flow pathway through the aqueduct was obstructed in many hydrocephalic rats. It is concluded that the hydrocephalus may be the result of abnormal brain development in the midline region of the dorsal mesencephalon, leading to aqueduct closure.