Variations In Cerebral Blood Flow Research Articles

Arterial spin labeling in small animals: Methods and applications to experimental cerebral ischemia

ASL enables noninvasive, quantitative monitoring of cerebral perfusion to be performed repeatedly over a period of hours. Thus, ASL is an attractive method for basic science studies of the time evolution and pathophysiology of diseases using animal models. In particular, ASL is valuable for basic science studies of evolving tissue status and viability in stroke using animal models of acute ischemia. This study describes both pulsed (PASL) and continuous ASL (CASL) studies of quantitative cerebral perfusion in rodent models of cerebral ischemia. Some technical factors pertinent to these studies are discussed, including a method for measuring arterial blood T(1) and double-echo PASL for measuring cerebral blood flow (CBF) and volume (CBV). Investigations of the CBF response to forebrain ischemia and reperfusion, and of regional variations in CBF and arterial transit time (ATT) are also discussed.

Control of end-tidal PCO 2 reduces middle cerebral artery blood velocity variability: Implications for physiological neuroimaging

Breath-by-breath variability of the end-tidal partial pressure of CO 2 (P et CO 2 ) has been shown to be associated with cerebral blood flow (CBF) fluctuations. These fluctuations can impact neuroimaging techniques that depend on cerebrovascular blood flow. We hypothesized that controlling P et CO 2 would reduce CBF variability. Dynamic end-tidal forcing was used to control P et CO 2 at 1.5 mm Hg above the resting level and to hold the end-tidal partial pressure of oxygen (P et O 2 ) at the resting level. Peak blood velocity in the middle cerebral artery (MCA) was measured by transcranial Doppler ultrasound (TCD) as an index of CBF. Blood velocity parameters and timing features were determined on each waveform and the variance of these parameters was compared between Normal (air breathing) and Forcing (end-tidal gas control) sessions. The variability of all velocity parameters was significantly reduced in the Forcing session. In particular, the variability of the average velocity over the cardiac cycle was decreased by 18.2% ( P < 0.001). For the most part, the variability of the timing parameters was unchanged. Thus, we conclude that controlling P et CO 2 is effective in reducing CBF variability, which would have important implications for physiologic neuroimaging.

Induction of mild hypothermia with infusion of cold (4 °C) fluid during ongoing experimental CPR

Introduction: Therapeutic hypothermia after resuscitation has been shown to improve the outcome regarding neurological state and to reduce mortality. The earlier hypothermia therapy is induced probably the better. We studied the induction of hypothermia with a large volume of intravenous ice-cold fluid after cardiac arrest during ongoing cardiopulmonary resuscitation (CPR). Methods: Twenty anaesthetised piglets were subjected to 8 min of ventricular fibrillation, followed by CPR. They were randomized into two groups. The hypothermic group was given an infusion of 4 °C acetated Ringer's solution 30 ml/kg at an infusion rate of 1.33 ml/kg/min, starting after 1 min of CPR. The control group received the same infusion at room temperature. All pigs received a bolus dose of vasopressin after 3 min of CPR. After 9 min, defibrillatory shocks were applied to achieve restoration of spontaneous circulation (ROSC). Core temperature and haemodynamic variables were measured at baseline and repeatedly until 180 min after ROSC. Cortical cerebral blood flow was measured, using Laser-Doppler flowmetry. Results: All pigs had ROSC, except one animal in the hypothermic group. Only one animal in the hypothermic group died during the observation period. The calculated mean temperature reduction was 1.6 ± 0.35 °C (S.D.) in the hypothermic group and 1.1 ± 0.37 °C in the control group ( p = 0.009). There was no difference in cortical cerebral blood flow and haemodynamic variables. Conclusion: Inducing hypothermia with a cold infusion seems to be an effective method that can be started even during ongoing CPR. This method might warrant consideration for induction of early therapeutic hypothermia in cardiac arrest victims.

Regional variability in the CBF response to mild hypotension correlates with heterogeneous CBF after focal cerebral ischemia

Regional variability in cerebral blood flow (CBF) during mild hypotension has been demonstrated (Kharlamov et al, Neurosci Lett 368: 151–156, 2004). We hypothesize that regional changes in CBF in response to hypotension can predict the CBF changes in the same brain after focal ischemia. Male Sprague/Dawley rats (n=4) were intubated and mechanically ventilated (0.5–1.5% isoflurane, 70% N2O balance O2). An 8-mm diameter closed cranial window was placed between bregma and lambda. Focal ischemia was produced by transection of the left MCA and bilateral common carotid artery occlusion (MCAT). Laser speckle flowmetry (LSF) allowed simultaneous measurement of CBF in different cortical regions. CBF was measured in at least 70 separate regions of interest (ROI, 310 microns diameter): a) before blood withdrawal at a mean arterial pressure (MAP) of 100 mmHg, CBF1; b) during hemorrhagic hypotension, MAP 70 mmHg, CBF2; c) after blood re-infusion and before MCAT at MAP 100 mmHg, CBF3; d) after MCAT at MAP 100 mmHg, CBF4. In each ROI, the response to hypotension and MCAT were expressed as %CBF70 [100*(CBF2/CBF1)] and %CBFMCAT [100*(CBF4/CBF3)], respectively. Using these percentages, ROIs were divided into three types (LF, NF, and HF) with the boundaries of 85% and 120%, and 45% and 120%, respectively. For each ROI, we analyzed changes in the CBF response from hypotension to MCAT between the categories LF, NF, and HF as presented in the Table. Analysis of CBF in individual animals demonstrated that in rats 1 and 2 (see Table 1) the total % of ROIs with the same level of response were 55 and 57%, respectively. In most of those ROIs the flow after ischemia remained in the NF category (53%). In another two rats the hypotension LF ROIs remained as LF after MCAT (61% and 42%). At 2 h after MCAT 5915% (n=4, mean STD) of ROIs remained in the same category as during mild hypotension, and 2515% (n=4, mean STD) reduced from NF ROIs during hypotension to LF after MCAT. ROIs with HF during hypotension either stayed in the same category or reduced to NF after MCAT, but never became LF. Therefore, regional changes of CBF during mild hypotension were predictive of the flow changes in the ischemic brain. Table 1

Regional Variation of Cerebral Blood Flow and Arterial Transit Time in the Normal and Hypoperfused Rat Brain Measured Using Continuous Arterial Spin Labeling MRI

Continuous arterial spin labeling (CASL) is a noninvasive magnetic resonance (MR) method for measuring cerebral perfusion. In its most widely used form, CASL incorporates a postlabeling delay to minimize the sensitivity of the technique to transit time effects, which otherwise corrupt cerebral blood flow (CBF) quantification. For this delay to work effectively, it must be longer than the longest transit time present in the system. In this work, CASL measurements were made in four coronal slices in the rat brain using a range of postlabeling delays. By doing this, direct estimation of both CBF and arterial transit time (delta(a)) was possible. These measurements were performed in the normal brain and during hypoperfusion induced by occlusion of the common carotid arteries. It was found that, in the normal rat brain, significant regional variation exists for both CBF and delta(a). Mean values of CBF and delta(a) in the selected gray matter regions of interest were 233 mL/100 g min and 266 ms, respectively, with the latter ranging from 100 to 500 ms. Therefore, use of a 500-ms postlabeling delay is suitable for any location in the normal rat brain. After common carotid artery occlusion, CBF decreased and delta(a) increased by regionally dependent amounts. In the sensory cortex, delta(a) increased to a mean value of 740 ms, significantly greater than 500 ms. These results highlight the importance of either (a) determining delta(a) as part of the CASL measurement or (b) knowing the approximate range of values delta(a) is likely to take for a given application, so that the parameters of the CASL sequence can be chosen appropriately.

Intersubject Variability and Reproducibility of 15O PET Studies

Oxygen-15 positron emission tomography (15O PET) can provide important data regarding patients with head injury. We provide reference data on intersubject variability and reproducibility of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolism (CMRO2) and oxygen extraction fraction (OEF) in patients and healthy controls, and explored alternative ways of assessing reproducibility within the context of a single PET study. In addition, we used independent measurements of CBF and CMRO2 to investigate the effect of mathematical correlation on the relationship between flow and metabolism. In patients, intersubject coefficients of variation (CoV) for CBF, CMRO2 and OEF were larger than in controls (32.9%+/-2.2%, 23.2%+/-2.0% and 22.5%+/-3.4% versus 13.5%+/-1.4%, 12.8%+/-1.1% and 7.3%+/-1.2%), while CoV for CBV were lower (15.2%+/-2.1% versus 22.5%+/-2.8%) (P<0.001). The CoV for the test-retest reproducibility of CBF, CBV, CMRO2 and OEF in patients were 2.1%+/-1.5%, 3.8%+/-3.0%, 3.7%+/-3.0% and 4.6%+/-3.5%, respectively. These were much lower than the intersubject CoV figures, and were similar to alternative measures of reproducibility obtained by fractionating data from a single study. The physiological relationship between flow and metabolism was preserved even when mathematically independent measures were used for analysis. These data provide a context for the design and interpretation of interventional PET studies. While ideally each centre should develop its own bank of such data, the figures provided will allow initial generic approximations of sample size for such studies.

Human cerebral circulation: positron emission tomography studies

We reviewed the literature on human cerebral circulation and oxygen metabolism, as measured by positron emission tomography (PET), with respect to normal values and of regulation of cerebral circulation. A multicenter study in Japan showed that between-center variations in cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) values were not considerably larger than the corresponding within-center variations. Overall mean +/- SD values in cerebral cortical regions of normal human subjects were as follows: CBF = 44.4 +/- 6.5 ml/100 ml/min; CBV = 3.8 +/- 0.7 ml/100 ml; OEF = 0.44 +/- 0.06; CMRO2 = 3.3 +/- 0.5 ml/100 ml/min (11 PET centers, 70 subjects). Intrinsic regulation of cerebral circulation involves several factors. Autoregulation maintains CBF in response to changes in cerebral perfusion pressure; chemical factors such as PaCO2 affect cerebral vascular tone and alter CBF; changes in neural activity cause changes in cerebral energy metabolism and CBF; neurogenic control of CBF occurs by sympathetic innervation. Regional differences in vascular response to changes in PaCO2 have been reported, indicating regional differences in cerebral vascular tone. Relations between CBF and CBV during changes in PaCO2 and during changes in neural activity were in good agreement with Poiseuille's law. The mechanisms of vascular response to neural activation and deactivation were independent on those of responses to PaCO2 changes. CBV in a brain region is the sum of three components: arterial, capillary and venous blood volumes. It has been reported that the arterial blood volume fraction is approximately 30% in humans and that changes in human CBV during changes in PaCO2 are caused by changes in arterial blood volume without changes in venous blood volume. These findings should be considered in future studies of the pathophysiology of cerebrovascular diseases.

Introduction of respiratory pattern generators into models of respiratory control

We have adapted two models previously proposed as respiratory pattern generators (RPGs) into a neurochemical feed back control model of ventilation. The RPG models, non-dimensional as originally presented, consisted of oscillating circuits of either two or five interconnected neurons [Matsugu, M., Duffin, J., Poon, C.-S., 1998. Entrainment, instability, quasi-periodicity, and chaos in a compound neural oscillator. J. Comput. Neurosci. 5, 35-51; Botros, S.M., Bruce, E.N., 1990. Neural network implementation of a three-phase model of respiratory rhythm generation. Biol. Cybern. 63, 143-153]. The neurochemical model into which they were integrated [Longobardo, G., Evangelisti, C.J., Cherniack, N.S., 2002. Effects of neural drives on breathing in the awake state in humans. Respir. Physiol. 129, 317-333] included the effects of cerebral blood flow variation with CO2, vagal stretch receptors input and a multicompartment model of carbon dioxide stores. The methodology is described whereby these neuronal oscillator networks were quantified, a necessary step for their inclusion as RPGs in broader models of the overall control of respiration. Subsequent simulations of the ventilation response to carbon dioxide with either respiratory pattern generator model exhibited only a limited range in which tidal volume and frequency increased with increasing respiratory drive. With both models, frequency peaked and then declined, as did ventilation when P CO2 was greater than normal. The range of the models was extended if the respiratory pattern generators were considered to be composed of multiple neuronal oscillators or a single oscillator in which there was increasing phasic input that was gated or pacemaker driven.

Patient-Triggered Ventilation: How Does the Trigger Work?

FOR THE VAST MAJORITY OF neonates requiring ventilation in our NICUs today, we use what is called patient-triggered ventilation (PTV)—synchronized intermittent mandatory ventilation, assist/control ventilation, or pressure support ventilation (Table 1). Also called synchronized ventilation, PTV has long been used successfully in adults. The goal of PTV is to prevent asynchronous breathing against the ventilator, which has been shown to contribute to pneumothorax in the neonate and subsequently to an increased risk of intraventricular hemorrhage in preterm infants.1,2Other short-term benefits of PTV include improvements in oxygenation and carbon dioxide elimination, reduced variability in cerebral blood flow, and a shorter duration of mechanical ventilation.3

Neuroprotective effect of γ-glutamylethylamide (theanine) on cerebral infarction in mice

In the present study, we examined the neuroprotective effect of γ-glutamylethylamide (theanine) on the ischemic brain damage in a middle cerebral artery occlusion model in mice. Theanine was injected i.p. 3 h after the occlusion or immediately before and 3 h after the occlusion. Theanine (1 mg/kg) significantly decreased the size of the cerebral infarcts 1 day after the occlusion. In contrast, theanine did not affect the cerebral blood flow, brain temperature and physiological variables (pH, pCO 2, pO 2 and hematocrit) in this model. These results suggest that theanine directly provides neuroprotection against focal cerebral ischemia and may be clinically useful for preventing cerebral infarction.

Low cerebral blood flow resistance in nonventilated preterm infants predicts poor neurologic outcome.

To examine whether cerebral blood flow variables during the first critical day of life can predict the 1-yr neurologic outcome in ventilated and nonventilated preterm infants. Prospective follow-up study. Neonatal intensive care unit of university central hospital. Forty-nine preterm infants <33 wks of gestation. Doppler ultrasound investigations of the brain circulation, heart rate, and systemic blood pressure were performed in ventilated (n = 35) and nonventilated (n = 14) preterm infants during the first day of life. The neurologic development was evaluated using Griffith's subscales at 12 months of corrected age. Cerebral blood flow velocity measurements were obtained from the anterior cerebral artery and internal carotid artery. Cerebral blood flow, cerebral blood flow resistance, and cerebral perfusion pressure subsequently were derived. These derived cerebral perfusion variables were associated with the sum of Griffith's developmental scales (p <.02). However, the slopes of regression lines between cerebral blood flow or cerebral blood flow resistance and the sum of Griffith's psychomotor developmental scales tended to be different in the ventilated and nonventilated infants (p =.06, p =.003, respectively). The correlations between these variables and the sum of Griffith's psychomotor developmental scales were significant only in nonventilated preterm infants (r =.69, p =.007, and r = -.85, p =.001, respectively). Our data suggest that lowered cerebral blood flow resistance reflecting lowered cerebral blood flow during early circulatory transition is associated with adverse outcome in nonventilated preterm infants, but no connection in ventilated infants was found.

Regional heterogeneity of cerebral blood flow response to graded pressure-controlled hemorrhage.

Little is known about the regional distribution of cerebral blood flow (CBF) in nonanesthetized animals during periods of lowered blood pressure. The present investigation addresses the specific reaction patterns of local cerebral blood flow (LCBF) in comparison with mean CBF during graded pressure-controlled hemorrhagic shock in conscious rats. Conscious rats were subjected to graded pressure-controlled hemorrhage (to 85, 70, 55, or 40 mm Hg) by arterial blood withdrawal. After a period of 30 minutes, blood pressure was stabilized by withdrawal or reinfusion of blood. LCBF was determined autoradiographically by the iodo(14C)antipyrine method in 34 brain structures, and mean CBF was calculated and compared with the values of nonhemorrhaged control animals. Mean CBF remained unchanged except for the group with the lowest blood pressure of 40 mm Hg (decrease in CBF of 28%). Otherwise, LCBF was increased in some brain structures at an unchanged mean CBF. Congruently, at 40 mm Hg, the decrease in mean CBF did not show up in all brain structures, the local pattern of CBF varying between an unchanged and a profoundly decreased CBF. The mean coefficient of variation of CBF was increased with the severity of hemorrhagic shock, which indicates an enhanced heterogeneity of CBF. Because of the substantial heterogeneity in the responses of LCBF to pressure-controlled hemorrhage, autoregulation of CBF during pressure-controlled hemorrhagic shock has to be reconsidered on a regional basis.

Sleep-related changes in the regulation of cerebral blood flow in newborn lambs.

The interplay between cerebral perfusion pressure (CPP) and vascular resistance leads to fluctuations in cerebral blood flow (CBF). The relationship between fluctuations in CBF and those in CPP provides insight into the impact of the regulation of vascular resistance on CBF. The aim of this work was to study sleep-related changes in CBF regulation in newborn lambs, by quantifying the extent to which variability in CBF is related to that of CPP in the different wake-sleep states. Repeated-measurement within-subject. 8 newborn lambs. Chronic instrumentation with electrodes (electrocorticogram, electrooculogram, nuchal electromyogram), an arterial catheter (arterial pressure), a subdural catheter (intracranial pressure), and an ultrasonic flow probe around the superior sagittal sinus (CBF). The CPP (difference between arterial and intracranial pressure) and CBF data sequences during quiet wakefulness, rapid-eye-movement (REM) sleep and non-REM sleep were subject to spectral analysis. The fraction of CBF variability explained by CPP variability (CPP vs CBF squared coherence in the range 0.05-0.3 Hz) was highest in REM sleep (0.653) and lowest in non-REM sleep (0.413). The CBF variability (coefficient of variation due to fluctuations in the range 0.05-0.3 Hz) was higher than CPP variability in all states, albeit not significantly in REM sleep. Results suggest that synchronized vasomotor fluctuations accounting for a quota of CBF variability not explained by CPP variability occur in all states in newborn lambs. Their relative contribution to CBF variability differs among wake-sleep states, being highest during non-REM sleep and lowest during REM sleep.

Database of normal human cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen measured by positron emission tomography with 15 O-labelled carbon dioxide or water, carbon monoxide and oxygen: a multicentre study in Japan

Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO(2)) by positron emission tomography (PET) with oxygen-15 labelled carbon dioxide (C(15)O(2)) or (15)O-labelled water (H(2)(15)O), (15)O-labelled carbon monoxide (C(15)O) and (15)O-labelled oxygen ((15)O(2)) is useful for diagnosis and treatment planning in cases of cerebrovascular disease. The measured values theoretically depend on various factors, which may differ between PET centres. This study explored the applicability of a database of (15)O-PET by examining between-centre and within-centre variation in values. Eleven PET centres participated in this multicentre study; seven used the steady-state inhalation method, one used build-up inhalation and three used bolus administration of C(15)O(2) (or H(2)(15)O) and (15)O(2). All used C(15)O for measurement of CBV. Subjects comprised 70 healthy volunteers (43 men and 27 women; mean age 51.8+/-15.1 years). Overall mean+/-SD values for cerebral cortical regions were: CBF=44.4+/-6.5 ml 100 ml(-1) min(-1); CBV=3.8+/-0.7 ml 100 ml(-1); OEF=0.44+/-0.06; CMRO(2)=3.3+/-0.5 ml 100 ml(-1) min(-1). Significant between-centre variation was observed in CBV, OEF and CMRO(2) by one-way analysis of variance. However, the overall inter-individual variation in CBF, CBV, OEF and CMRO(2) was acceptably small. Building a database of normal cerebral haemodynamics obtained by the(15)O-PET methods may be practicable.

Precision of the CASL-perfusion MRI technique for the measurement of cerebral blood flow in whole brain and vascular territories.

To analyze the precision of cerebral blood flow (CBF) measurements made with continuous arterial spin labeling(CASL) perfusion magnetic resonance imaging (MRI) over experimentally relevant intervals. CASL perfusion MRI measurements of CBF on a 1.5-T GE Signa magnet were repeated in young healthy male and female subjects at one hour and one week. Precision of the measurement was evaluated at both time intervals. CASL perfusion MRI measurements of CBF yielded within-subject coefficients of variation (wsCV) of 5.8% for global and 13% for individual vascular regions when measurements were repeated within one hour. Differences in these values represent the error in post-processing. Global and regional CBF measurements over one week yielded wsCVs of 13% and 14%, respectively. At one week, error secondary to physiologic variability affected global and regional measurements to the same degree and masked the software post-processing error seen at one hour. The magnitude of the difference in repeated measures correlated with the magnitude of the measurement. CASL perfusion MRI CBF measurements are accurate and precise. Variability over longer periods of time appears attributable to physiologic factors. Repeatability of the CASL measurement is sensitive to the magnitude of the measurement. This should be taken into account when studies requiring repeated measures involve subjects with significant variability in CBF.

A theoretical model of oxygen delivery and metabolism for physiologic interpretation of quantitative cerebral blood flow and metabolic rate of oxygen.

The coupling of cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO2) during physiologic and pathophysiologic conditions remains the subject of debate. In the present study, we have developed a theoretical model for oxygen delivery and metabolism, which describes the diffusion of oxygen at the capillary-tissue interface and the nonlinear nature of hemoglobin (Hb) affinity to oxygen, allowing a variation in simple-capillary oxygen diffusibility, termed "effective oxygen diffusibility (EOD)." The model was used to simulate the relationship between CBF and CMRO2, as well as oxygen extraction fraction (OEF), when various pathophysiologic conditions were assumed involving functional activation, ischemia, hypoxia, anemia, or hypo- and hyper-capnic CBF variations. The simulations revealed that, to maintain CMRO2 constant, a variation in CBF and Hb required active change in EOD. In contrast, unless the EOD change took place, the brain allowed small but significant nonlinear change in CMRO2 directly dependent upon oxygen delivery. Application of the present model to quantitative neuroimaging of CBF and CMRO2 enables us to evaluate the biologic response at capillary level other than Hb- and flow-dependent properties of oxygen transport and may give us another insight regarding the physiologic control of oxygen delivery in the human brain.

Blood flow activation in rat somatosensory cortex under sciatic nerve stimulation revealed by laser speckle imaging*

Abstract In many functional neuroimaging research the change of local cerebral blood flow (CBF) induced by sensory stimulation is regarded as an indicator of the change in cortical neuronal activity although a precise and full spatio-temporal description of local CBF response coupled to neural activity has still not been laid out. Using the laser speckle imaging technique a relatively large exposed area in somatosensory cortex of rat was imaged for the observation of the variations of CBF during sciatic nerve stimulation. The results showed that cerebral blood flow activation was spatially localized and discretely distributed in the targeted microvasculature. Individual arteries, veins and capillaries in different diameters were activated with the time going. The response pattern of CBF related to the function of brainactivity and energy metabolism is delineated exactly.

Cortical blood flow autoregulation revisited using laser Doppler perfusion imaging.

Methods of laser Doppler perfusion monitoring (LDPM) and imaging (LDPI) have been validated and found useful for measurements of brain blood flow in several studies. The present work was undertaken to examine the cortical blood flow autoregulatory phenomenon as it has lately been questioned and claimed to be method-dependent and related to sample volume. Spatial variations in cerebral cortical blood flow (CBF(cortex)) in the pressure range 20-140 mmHg (static cerebral autoregulation; caval block/angiotensin infusion) were studied in six mechanically ventilated (hypocapnic, normocapnic and hypercapnic) pigs anaesthetized with propofol and fentanyl. Although the cortical blood flow values sampled were highly heterogeneously distributed, they were strongly pressure-dependent as well as CO2-dependent (P < 0.001). A cumulative cerebral blood flow (CBF)-pressure (MAP) plot comprising all values obtained indicated a pressure range between 70 and 120 mmHg where CBF remained almost constant. However, at the local level in the cortex (mm2) the same type of 'classic' autoregulatory flow : pressure graphs (FPG) were found in only a few of the cases of the cortical areas examined (n = 96). Alterations in blood P(a)CO2 saturation did not affect the pressure : flow relationship at low perfusion pressures, whereas at normal or above normal values, and as anticipated, hypercapnia considerably increased CBF (P < 0.001). 'Classic' autoregulatory FPGs were found only when all values sampled were clustered together, whereas, as a new finding, data are presented indicating that autoregulatory capacity is lacking at the local level at some cortical surface areas.

Dynamic variations of local cerebral blood flow in maximal electroshock seizures in the rat.

Measurement of cerebral blood flow is routinely used to locate the areas involved in generation and spread of seizures in epilepsy patients. Because the nature of the hyperperfused regions varies with the timing of injection of tracer, in this study, we used a rat model of maximal electroshock seizures to follow up the time-dependent changes in the distribution of seizure-induced cerebral blood flow (CBF) changes. CBF was measured by the quantitative autoradiographic [14C]iodoantipyrine technique over a 30-s duration. The tracer was injected either at 15 s before seizure induction, simultaneous with the application of the electroshock (tonic phase), at the onset of the clonic phase, or at 3 and 6 min after the seizure (postictal phase). Rates of CBF underwent dynamic changes during the different phases of seizure activity and largely increased over control levels (< or =400%) in the 45 regions studied during all phases of the seizure (first 3 times). CBF remained higher than control levels in 35 and 15 areas at 3 and 6 min after the seizure, respectively. The distribution of maximal CBF increases showed a good correlation with their known involvement in the circuits underlying the clinical expression of the different types of seizure activity, tonic versus clonic.

Protective Effect of Spinal Cord Stimulation on Experimental Early Cerebral Vasospasm

In this study we investigate the effects of cervical spinal cord stimulation (cSCS) on experimental ‘early spasm’ in rabbits as described in personal previous experience (Acta Neurochir 2001;143:177–185). Twenty-four adult red Burgundy rabbits wearing a cervical epidural electrode underwent cerebral blood flow (CBF) and functional monitoring of early basilar spasm before and during cSCS. CBF changes, as a consequence of cSCS, occurred in 20 control animals. No CBF changes, consistent with no basilar artery vasospasm, occurred after subarachnoid haemorrhage (SAH) up to the end of the experiments in all the stimulated animals. The role of reversible functional sympathectomy in mediating the effect of spinal cord stimulation on early spasm is discussed. cSCS is able to prevent ‘early spasm’ due to SAH in all the animals studied, independently from the occurrence and the sign of stimulation induced CBF variations.