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Effect of propofol on the electrocorticogram in epileptic patients undergoing cortical resection.

We have compared the effect of clinical doses of propofol with thiopental on epileptiform activity in the electrocorticograms (ECoG) of 20 epileptic patients undergoing temporal lobe resection. After baseline ECoG had been obtained, with inspired concentrations of 0.5-1% isoflurane and 70% nitrous oxide to provide background anaesthesia, subjects were allocated randomly to receive boluses of either thiopental 25 mg or propofol 20 mg i.v. every 30 s to a maximum of 5 mg kg-1 or until burst suppression was seen. The ECoG was recorded throughout administration and for 10 min thereafter. After return of baseline ECoG tracings, the alternate agent was administered. The amount of epileptiform activity was recorded on an ordinal rating scale, an increase being indicated by either a rise of at least one category on the scale or discharges occurring at a minimum of one new site. Activation occurred more frequently with thiopental but the difference was not significant. This study suggests that propofol has no greater proconvulsive effect than thiopental, a drug commonly used in managing status epilepticus.

Adolescent↗

Origin and propagation of interictal discharges in the acute electrocorticogram. Implications for pathophysiology and surgical treatment of temporal lobe epilepsy.

Although acute electrocorticography (ECoG) is routinely performed during epilepsy surgery there is little evidence that the extent of the discharging regions is a useful guide to tailoring the resection or that the findings are predictive of outcome or pathology. Patterns of discharge propagation have, however, rarely been considered in assessing the ECoG. We hypothesize that regions where discharges show earliest peaks ('leading regions') are located in the epileptogenic zone, whereas sites in which late, secondary, propagated activity occurs have less epileptogenic potential and do not need to be excised. To allow intraoperative topographic ECoG analysis, a computer program has been developed to identify leading regions and the sites showing greatest rates or amplitudes of spikes. Their topography has been compared retrospectively with pathology and seizure control in 42 consecutive patients following temporal lobe surgery. Leading regions were most often found in the hippocampus, the subtemporal cortex and the superior temporal gyrus. The most common propagation patterns were from hippocampus to subtemporal cortex and vice versa. There was no association between seizure outcome and the location of regions with greatest incidence or amplitude of spikes or location of leading regions. There was, however, a strong and significant association between poor outcome and non-removal of leading regions other than those in the posterior subtemporal cortex. All leading regions (other than posterior subtemporal) were resected in 27 patients of whom 25 had a favourable outcome. Leading regions (other than posterior subtemporal) remained in 14 patients of whom only four had a good outcome. One patient had no epileptiform activity in the ECoG and good outcome. Persistent posterior subtemporal leading regions remained in nine subjects; all had favourable outcome (Grades I or II) but only three were seizure free. These results suggest that: (i) interictal epileptiform discharges may originate from a complex interaction between separate regions, resulting in propagation and recruitment of neuronal activity along specific neural pathways; (ii) removal of all discharging areas appears unnecessary to achieve seizure control provided that leading regions (other than posterior subtemporal) are removed; and (iii) identification of such leading regions could be used to tailor resections in order to improve seizure control and reduce neurological, neuropsychological and psychiatric post-surgical morbidity.

Adolescent↗

Epilepsy surgery involving the sensory-motor cortex.

Our aim was to assess the outcome with regard to seizures and neurological function in unselected patients undergoing resective surgery involving the perirolandic area, with or without multiple subpial transections (MSTs). All patients who underwent perirolandic cortical resection or MSTs from 1979 to 2003 at the London Health Sciences Centre were identified. Patients were included if they had seizures originating in the perirolandic area, recorded with subdural electrodes, or if they had scalp recorded seizures and a congruent discrete epileptogenic lesion on MRI in the perirolandic area. Most patients had electrocorticography (ECoG) at the time of surgery. Data collected include pre-operative and post-operative neurological deficits, MRI findings, interictal and ictal scalp EEG, interictal and ictal subdural data, ECoG findings, type and extent of surgery, neuropathologic diagnoses, and seizure outcomes. We studied 52 patients (22 females). The average age at the time of surgery was 33 years, and the average post-operative follow-up was 4.2 years. The most frequent aetiologies were neoplastic in 26 patients (50%), vascular in eight (15%), malformations of cortical development in six (12%), Rasmussen's encephalitis in three (6%) and other aetiologies in nine (17%). Surgery involved the pre-central gyrus in 17 patients, pre- and post-central gyrus in 13, the inferior central region in 11, the post-central gyrus in 7, and the pre-central gyrus and mesial frontal area in 2. At last follow-up 16 patients were in Engel class I (31%), 8 (15%) in class II, 14 (27%) in class III and 14 (27%) in class IV. Residual neurological deficits were present in 26 patients (50%), occurred more frequently in patients > or =25 years old (P < 0.05) and were mild in 14 (54%) patients. In univariate analyses, better seizure outcomes (P < 0.05) occurred in patients whose ECoG showed infrequent post-resectional spikes and no spikes distant to the resection margin, and in resections involving the pre-central and inferior rolandic cortex. In unselected patients with intractable perirolandic epilepsy, many of whom have large, complex epileptogenic lesions, various levels of seizure improvement can be achieved in almost 75% through well-planned surgical resections. New, severe post-operative neurological deficits can occur in 23% of these patients and appear to be more frequent in older patients. Whereas scalp EEG provided limited information to guide surgery, findings on interictal ECoG predicted seizure outcome.

Action Potentials↗

A comparison of cerebral ischemic flow thresholds during halothane/N2O and isoflurane/N2O anesthesia in rats.

Isoflurane/N2O anesthesia has been reported to reduce the cerebral blood flow (CBF) threshold at which electroencephalographic changes occur in humans during carotid occlusion (when compared to halothane/N2O). To further evaluate this observation, normocapnic, normothermic rats were anesthetized with 0.75 MAC isoflurane or halothane in combination with 60% N2O. The electrocorticogram (ECoG) and the cortical DC potential were recorded using glass microelectrodes. Both carotid arteries were occluded, and mean arterial pressure (MAP) was reduced over 3-5 min (by phlebotomy) to predetermined values between 30 and 75 mmHg. This MAP was maintained for 10 min, and CBF was then measured in cortical gray matter using [3H]-nicotine. Flows were then correlated with ECoG changes and with the presence or absence of cortical depolarization (which reflects the loss of transmembrane ion homeostasis). In other rats, the cortical cerebral metabolic rate for glucose (CMRglu) was determined autoradiographically using [14C]-deoxyglucose. Finally, the time to depolarization was determined in rats killed with KCl and in rats subjected to hypotension (MAP = 30-35 mmHg) followed by abrupt bilateral carotid occlusion. The distributions of CBF values in the anesthetic groups were essentially identical. The incidence of either major ECoG changes or isoelectricity did not differ between anesthetics. The CBF associated with major ECoG changes (excluding isoelectricity) were 35 +/- 12 and 39 +/- 18 ml.100 g-1.min-1 in the halothane/N2O and isoflurane/N2O groups respectively (mean +/- SD, difference not significant [NS]). Isoelectricity was seen at 7 +/- 4 ml.100 g-1.min-1 (median = 6.5) with halothane/N2O and 17 +/- 19 ml.100 g-1.min-1 (median = 11) with isoflurane/N2O (again, NS). The incidence of sustained depolarization did not differ between anesthetics (9 of 25 for halothane/N2O, 8 of 24 with isoflurane/N2O). CBF associated with sustained depolarization was 13 +/- 12 ml.100 g-1.min-1 (median = 10) with halothane/N2O, compared with 9 +/- 6 ml.100 g-1.min-1 (median = 9) for isoflurane/N2O (NS). In rats subjected to cardiac arrest, the time to depolarization was longer with isoflurane/N2O (102 +/- 19 s vs. 77 +/- 7 s). In rats subjected to carotid occlusion at a MAP = 30-35 mmHg, the time to depolarization was again longer with isoflurane/N2O (210 +/- 78 s vs. 122 +/- 44 s). Cortical CMRglu was lower with isoflurane/N2O (25 +/- 5 mumol.100 g-1.min-1) than with halothane (43 +/- 13 mumol.100 g-1.min-1, P = 0.03). The results indicate that isoflurane/N2O anesthesia delays the onset of ischemic cell depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia, Inhalation↗

Alfentanil-induced epileptiform activity in patients with partial epilepsy.

We performed a retrospective study investigating the effect of alfentanil hydrochloride on electrocorticography (ECoG) in 23 patients with intractable nonlesional partial epilepsy undergoing anterior temporal lobectomies at this institution. Alfentanil is a short-acting, parenteral, opioid analgesic with a rapid onset of action. Opioid drugs have the potential to induce hippocampal electrographic seizures. Pre-excision ECoG was obtained before and after the administration of 50 micrograms/kg of alfentanil. ECoG was performed using subdural strips placed on the lateral temporal surface and in the suprasylvian region and monopolar depth electrodes implanted into the amygdala and hippocampus. The surgically excised temporal lobes revealed cortical gliosis and varying degrees of hippocampal neuronal loss in all patients. A quantitative assessment of the effect of alfentanil on the ECoG was performed by measuring the frequency of interictal spikes. There was a significant increase in the mesial temporal lobe mean spike frequency after the administration of alfentanil (p < 0.001). One patient had an alfentanil-induced mesial temporal lobe electrographic seizure. Alfentanil did not have a significant effect on spike activity in the suprasylvian region (p = 0.500). Further studies will be necessary to determine the specificity of alfentanil activation in patients with partial seizures of temporal lobe origin.

Adolescent↗

Continuous electrocorticogram epileptiform discharges due to brain gliosis.

Cortical dysplasia is known to produce continuous epileptiform discharges (CEDs) on electrocorticogram (EcoG) and EEG recordings. The authors studied the incidence of CEDs on ECoGs and correlated this data with pathologic findings. Thirty ECoGs were reviewed that were performed on patients with parietal or occipital lobe epilepsy operated on since 1960. CED was classified as: (1) continuous or semicontinuous rhythmic spikes or sharp waves at frequencies ranging from 2 to 8 Hz, and (2) repetitive bursts of rhythmic polyspike activity lasting 2 to 10 s. All nontumoral pathologic specimens were reviewed. Epileptiform activity was classified using the following criteria: focal (one gyrus), regional (two gyri), lobar (three gyri), bilobar, or multilobar. Pathologic examination showed gliosis in eight specimens, focal cortical dysplasia in five specimens, tumoral lesions in eight specimens, and other pathology in nine specimens. CED was found in 11 ECoGs. In seven pathology specimens, significant gliosis was shown, and in the remaining four specimens, a dysplastic lesion was diagnosed. Epileptiform activity was widespread (lobar, bilobar, or multilobar) when gliosis or focal cortical dysplasia was present. Absence of epileptiform activity or a focal/regional distribution was found in tumors and other lesions. These data suggest that extensive gliotic lesions are highly epileptogenic and produce CEDs, which are morphologically undistinguishable from those produced by focal cortical dysplasia.

Brain Diseases↗

Electrocochleographic and audiometric evaluation of hypobaric effect in Meniere's disease.

OBJECTIVES: To elucidate the effects of hypobaric pressure on cochlear hydrodynamics in patents with well-defined Meniere's disease. DESIGN: Sixteen patients were consecutively selected. Elevated hearing threshold levels and pathological transtympanal electrocochleography (tt-ECOG) were confirmed at the day of trial. The patients were exposed to repeated episodes of hypobaric pressure in a pressure chamber. The rate (20 daPa/s) and magnitude (-285 daPa) of chamber pressure change were low. The induced tympanic overpressure (+185 daPa) was continuously monitored and any tympanic equilibration was avoided. METHODS: The results of Bekesy and speech audiometry as well as tt-ECOG performed immediately before and after exposure were compared. The importance of chamber pressure change, number of hypobaric episodes, duration of exposure, and the induced relative tympanic overpressure was tested. RESULTS: It is shown that the relative tympanic overpressure is the most important factor to affect the cochlear hydrodynamics. Higher relative overpressure was associated with improvement of hearing threshold levels, while the ECOG results tended to improve with lower induced tympanic overpressure. CONCLUSION: The importance of tympanic overpressure shown in this study is in agreement with previous findings from hypobaric animal experiments. The inverse relation of psychoacoustic and ECOG tests suggests that the two methods evaluate different parameters, perhaps contributing differently to the physiology of hearing.

Adult↗

Meniere's disease: the incidence of hydrops in the contralateral asymptomatic ear.

OBJECTIVE: This study analyzes the incidence of endolymphatic hydrops in the asymptomatic contralateral ear of patients with classic Meniere's disease. STUDY DESIGN: A retrospective study of 3000 subjects who underwent electrocochleography (ECOG) from 1988 to 1998. METHODS: The presence of endolymphatic hydrops was determined by use of ECOG recordings, which were made through a transtympanic recording needle situated in the round window niche. Analysis was made of the 1-kHz toneburst summation potential (SP), and comparison was made between asymptomatic contralateral "Meniere's ears" (n = 144) and asymptomatic normal "control ears" (n = 114). RESULTS: Results demonstrated that more than 10% of the contralateral asymptomatic Meniere's ears have an ECOG recording that is highly suggestive of the presence of endolymphatic hydrops. In contrast, less than 2% of the control population demonstrate abnormal ECOG recordings. Furthermore, 15% of the population of contralateral Meniere's ears lie above the 95th percentile of the control population for 1-kHz tone-burst (100 dB) SP negativity. CONCLUSIONS: This study suggests that a high percentage of patients who have what appears to be unilateral Meniere's disease have evidence of endolymphatic hydrops in the contralateral asymptomatic ear. This finding has important clinical relevance for the management of patients in whom destructive surgery is planned and further highlights the importance of electrocochleography in the diagnosis and management of this disease process.

Audiometry, Evoked Response↗

The predictive value of intraoperative electrocorticography in resections for limbic epilepsy associated with mesial temporal sclerosis.

OBJECTIVE: Prior studies on the predictive value of intraoperative electrocorticography (ECoG) have been performed on heterogeneous groups of patients with both temporal and extratemporal interictal spikes, lesional and nonlesional pathological findings, and variably extensive resections by different surgeons. METHODS: We performed both pre- and postresection intraoperative ECoG on 29 consecutive patients with medial temporal lobe epilepsy (17 left-sided) who underwent standard nontailored resections by one surgeon (RRG). All patients had only temporal interictal spikes (six bitemporal) and mesial temporal sclerosis diagnosed by preoperative magnetic resonance imaging and confirmed by pathological examination of resected tissue. RESULTS: After a mean follow-up of 24.8 months, there were 15 (52%) patients who were seizure-free, 6 (21%) who were seizure-free except for auras, and 8 (28%) who had any seizure after the 1st postoperative month. Fourteen patients (48%) had active interictal discharges outside the area of planned resection revealed by preresection ECoG. Neither the presence of these spikes nor their mean frequency correlated with seizure outcome. Eleven patients (38%) had residual spike discharges after resection, and 18 patients (62%) had new spikes revealed by the postresection ECoG. Neither of these findings nor the mean spike frequency of residual or new spikes related to seizure outcome. Persistent spikes increased in frequency after resection in all outcome groups. CONCLUSIONS: Electrocorticographic monitoring of interictal epileptiform activity intraoperatively is not useful in the surgical treatment of patients undergoing standard resection for medial temporal lobe epilepsy with magnetic resonance imaging evidence of mesial temporal sclerosis.

Adolescent↗

Effects of sevoflurane on electrocorticography in patients with intractable temporal lobe epilepsy.

Fentanyl-droperidol technique is the choice for epilepsy surgery. It requires intraoperative electrocorticography (ECoG), but a large dose of fentanyl is needed for this technique. On the other hand, sevoflurane reportedly may be beneficial for intraoperative ECoG. To reveal whether the combined technique with fentanyl and sevoflurane is beneficial for epilepsy surgery, we investigated ECoG in 10 patients with intractable temporal lobe epilepsy without sevoflurane, with 0.5 minimum alveolar concentration (MAC) sevoflurane, and with 1.5 MAC sevoflurane under fentanyl-based anesthesia. The mean number of spikes for 1 minute decreased from 38.3 to 14.1 after 1.5 MAC sevoflurane was induced, which was statistically significant ( P <.05). Our results showed that balanced technique with neurolepto-analgesia (NLA) and sevoflurane is not suitable for epilepsy surgery requiring intraoperative ECoG. When epilepsy surgeries are performed under sevoflurane anesthesia, it is important to consider that sevoflurane may suppress electric activities when it is used with other anesthetic agents.

Adjuvants, Anesthesia↗

Dexmedetomidine sedation during awake craniotomy for seizure resection: effects on electrocorticography.

Patients with refractory seizures may undergo awake craniotomy and cortical resection of the seizure area, using intraoperative functional mapping and electrocorticography (ECoG). We used dexmedetomidine in 6 patients, transitioning successively from the asleep-awake-asleep method, through a combined propofol/dexmedetomidine sedative infusion, to dexmedetomidine as the only sedation. Initial experience with the asleep-awake-asleep method in 2 patients was successful with the replacement of propofol/laryngeal mask anesthesia, 20 to 30 minutes before ECoG testing, by dexmedetomidine infusion, maintained at 0.2 mcg kg-1 h-1 throughout neurocognitive testing. Propofol anesthesia was reintroduced for resection. One patient received combined dexmedetomidine (0.2 mcg kg-1 h-1) and propofol (200 mcg kg-1 min-1) infusions for sedation. Both infusions were stopped 15 minutes before ECoG. Subsequently, they were restarted and the epileptic foci resected. Three patients received dexmedetomidine as the sole sedative agent, together with scalp block local anesthesia, and incremental boluses totaling 150 to 175 mcg of fentanyl per case. Dexmedetomidine was started with 0.3 mcg kg-1 boluses and maintained with 0.2 to 0.7 mcg kg-1 h-1for craniotomy, testing, and resection. The infusion was paused for 20 minutes in 1 patient to allow improvement in neurocognitive testing. This occurred within 10 minutes. All patients enjoyed good hemodynamic control, with blood pressure maintained within 20% of initial values, and made uneventful recoveries. The surgical conditions were all reported as favorable. Dexmedetomidine can be used singly for sedation in awake craniotomy requiring ECoG. Individual dose ranges vary, but a bolus of 0.3 mcg kg-1 with an infusion of 0.2 mcg kg-1 min-1 is a good starting point, allowing accurate mapping of epileptic foci and subsequent resection.

Adolescent↗

Cortical resection with electrocorticography for intractable porencephaly-related partial epilepsy.

PURPOSE: We evaluated the results of cortical resection of epileptogenic tissue for treatment of intractable porencephaly-related epilepsy. METHODS: We examined clinical features, electrophysiological data, surgical findings, and seizure outcomes after cortical resection in eight patients with intractable epilepsy related to porencephalic cysts. RESULTS: All eight patients had hemiparesis. Five retained motor function in the hemiparetic extremities; six retained visual fields. All had partial seizures, six with secondary generalization. Seven patients had simple and three had complex partial seizures (CPSs); two also had drop attacks. Four patients had multiple seizure types. Long-term scalp video-EEG (LVEEG) localized interictal epileptic abnormalities that anatomically corresponded to the cyst location in three patients. LVEEG recorded ictal-onset zones in five; these anatomically corresponded to the cyst location in three of the five. EEG recorded generalized seizures in two patients, hemispheric in one, and multifocal in two. Intraoperative electrocorticography (ECoG) revealed interictal epileptic areas extending beyond the margins of the cyst in seven patients. We resected ECoG-localized interictal epileptic areas completely in five patients and partially in two. Cortical resection was based on seizure semiology and LVEEG in one patient whose ECoG showed no epileptiform discharges. After a minimum follow-up of 1 year, six patients had excellent seizure outcome (Engel class I), and two had a >90% seizure reduction (Engel class III) without complications. CONCLUSIONS: Cortical resection guided by ECoG allows preservation of motor function and visual field and provides an effective surgical procedure for treatment of intractable epilepsy secondary to porencephaly.

Adolescent↗

Features of seizures and behavioral changes induced by intrahippocampal injection of zinc sulfate in the rabbit: a new experimental model of epilepsy.

Seizure produced by intrahippocampal injection of zinc sulfate in rabbits is a new chronic model of experimental epilepsy. In this model, the clinical manifestations are easily observed and are expressed not only as partial clonic seizures, but also by secondary generalized seizures. The electrohippocampalogram (EHG) and electrocorticogram (ECoG) discharges change correspondingly during both types of seizures, and last for weeks. The mechanism for induced seizures may be partly related to the inhibitory effect of zinc sulfate injections on the acetylcholinesterase (AchE) activity in the hippocampus. The commonly used antiepileptic drugs, such as phenobarbital and phenytoin, afforded protection against the zinc-induced secondary generalized clonic seizures and alleviated the partial clonic seizures but had no influence on the EHG- and ECoG-monitored periodic bursts of spike discharges. Nitrazepam was found to antagonize both types of seizures and also transiently restored the EHG and ECoG to normal. D-penicillamine, a metal chelator, may be the most effective agent for the treatment of zinc-induced seizures; the agent, in addition to affording protection against both types of seizures, also caused the periodic burst spike discharges in EHG and ECoG to disappear.

Animals↗

Methohexital activation of epileptogenic foci during acute electrocorticography.

Methohexital was used as an activating agent in 62 patients undergoing focal cortical resections of epileptogenic foci and in six patients undergoing chronic electroencephalogram (EEG)/video monitoring with intracranial strip electrodes. In 87% of cases, methohexital caused selective activation of the epileptogenic focus during acute electrocorticography (ECoG). This activation appeared to be specific for the epileptogenic focus and did not cause epileptiform spiking from adjacent nonepileptogenic cortex. This ECoG activation occurred whether patients received local or general anesthesia. Sixty-five percent of patients demonstrated adequate activation with as little as 25 mg of drug. Methohexital is a safe and reliable method of activating epileptogenic foci during acute ECoG recordings and can decrease the time for ECoG recordings during surgery.

Brain↗

Electrocorticography and temporal lobe epilepsy: relationship to quantitative MRI and operative outcome.

We investigated the relationship between electrocorticography (ECoG), quantitative magnetic resonance imaging (MRI), and surgical outcome in 165 patients with intractable nonlesional temporal lobe epilepsy (NLTLE). A standard mesial temporal resection was performed in all patients. Patients with an operative follow-up < 1 year were excluded from the study. The extent of the lateral temporal neocortex resection (LCR) was guided by ECoG and the side of surgery. The extent of the LCR was not predictive of seizure outcome in patients with or without hippocampal formation atrophy (p > 0.5). Patients undergoing a right anterior temporal lobectomy had a larger LCR (p < 0.0001), but the side of surgery was not of predictive value in determining seizure outcome (p > 0.1). The topography of the acute intracranial spikes did not correlate with operative outcome (p > 0.5) and was independent of hippocampal volumetric studies (p > 0.5). The postexcision ECoG was also shown not to be of prognostic importance (p > 0.5). Our results indicates that the extent of the lateral temporal cortical resection and the ECoG findings are not important determinants of surgical outcome in patients with NLTLE.

Adolescent↗

The influence of prostacyclin on the recovery of bioelectric cerebral activity after complete ischemia.

Complete cerebral ischemia (CCI) was evoked by closing the brachiocephalic trunk, the left subclavicular artery and both internal thoracic arteries with simultaneous depression of systemic arterial pressure (SAP) to 70-50 mm Hg. The experiments were performed with three groups of rabbits. The first group consisted of animals with 15 and 20 min CCI, not receiving PGI2. In the second group PGI2 was given for 15 min before and during 15 min CCI. The third group with 15 and 20 min CCI received PGI2 3 min before, during and for 15 min after ischemia. The recovery of ECoG and the activities of the respiratory and vasomotor centres were evaluated as were reflex reactions. In 38 percent of the second group of rabbits improvement of the neurological condition after CCI was noted, as compared with animals of the control groups and a faster recovery of the ECoG. In the third group the neurological state improved in 100 percent of cases with simultaneous significantly quicker recovery of the first symptoms of brain cortex bioelectric activity and continuous activity in ECoG records. Between groups 1 and 2, and group 3 there were differences concerning the time of recovery of ECoG, and the intensity of reflexes. The influence of PGI2 on the brain bioelectric activity of the animals after CCI was found to be favourable.

Animals↗

Stimulation of breathing movements by L-5-hydroxytryptophan in fetal sheep during normoxia and hypoxia.

1. In fetal lambs in late gestation, systemic infusion of L-5-hydroxytryptophan (L-5-HTP) during normoxia greatly increases the incidence of fetal breathing movements (FBM) and high-voltage electrocortical activity (HV ECoG). It also induces FBM during HV ECoG and increases blood pressure. To investigate its mechanism of action, L-5-HTP was administered in conjunction with the 5-hydroxy-tryptamine (5-HT) antagonists ketanserin or cyproheptadine. L-5-HTP was also infused with or without the antagonists during hypoxia, to test whether it would overcome the inhibition of FBM by hypoxia. 2. When L-5-HTP was given in normoxia, cyproheptadine blocked and ketanserin reduced the increase in blood pressure, both drugs blocked the stimulation of FBM, but neither drug prevented the induction of prolonged episodes of HV ECoG. 3. In hypoxia, L-5-HTP similarly stimulated FBM. This effect was also blocked by cyproheptadine and was delayed by ketanserin. 4. The antagonism of the effects of L-5-HTP on blood pressure and the incidence of FBM in normoxia and hypoxia is consistent with the action of L-5-HTP via 5-HT receptors. At present there is no clear explanation of the mechanism by which L-5-HTP induces HV ECoG.

5-Hydroxytryptophan↗

Blood flow-dependent functional recovery in a rat model of focal cerebral ischemia.

The reduction in focal infarct volume after L-arginine has been attributed to an increase in regional cerebral blood flow (rCBF) within ischemic tissue. We tested the hypothesis that L-arginine-induced rCBF increases precede the recovery of spontaneous electrical activity [electrocorticogram (ECoG)] in spontaneously hypertensive rats subjected to middle cerebral artery (MCA) occlusion. ECoG was recorded from the penumbral region of parietal cortex by a glass microelectrode inserted into 1-mm3 cortical tissue from which blood flow was sampled by laser-Doppler flowmetry. rCBF dropped to 21 +/- 8% of the preischemic level, and ECoG was depressed by 64 +/- 13% after distal MCA occlusion. L-Arginine infusion (300 mg/kg i.v.) increased rCBF in 14 out of 18 rats, and ECoG significantly recovered in seven rats in which rCBF exceeded 31% of preischemic flow. Increases in rCBF anticipated the functional improvement in every case. Saline (n = 6) or D-arginine (n = 5) administration was ineffective. These data demonstrate that increasing rCBF can promote functional recovery in the ischemic brain and suggest that early administration of L-arginine or other vasodilators may enhance tissue survival by increasing rCBF.

Animals↗