4-vessel Occlusion Research Articles

Effect of Buchang naoxintong on plasma and cerebra argininevaso pressin levels in vascular dementia rats

目的 观察步长脑心通对血管性痴呆(VD)大鼠血浆、不同脑区精胺酸加压素(AVP)含量的影响,探讨其治疗VD的作用机理.方法 改良Pulsinellis四血管阻断法建立VD模型,采用穿梭箱系统检测大鼠学习记忆功能,放免法测定血浆及大脑皮质、下丘脑和海马AVP的含量.结果 中、西药组大鼠AAR比率[(63.5±5.0),(69.5±5.1),(70.0±5.6);(64.5±5.0),(68.2±5.7),(71.7±5.4)]显著高于模型组[(51.5±4.0),(42.5±4.6),(42.5±4.6)](P＜0.01),2治疗组间差异无显著性(P＞0.05).在大脑皮质、下丘脑和海马,中、西药组AVP含量[(5.01±0.25)pg/mg,(12.02±1.71)pg/mg,(5.57±0.22)pg/mg;(4.42±0.34)pg/mg,(9.86±1.76)pg/mg,(5.64±0.16)pg/mg]较模型组显著增多(P＜0.01);在大脑皮质、下丘脑,中药组AVP含量[(5.01±0.25)pg/mg,(12.02±1.71)pg/mg]显著高于西药组(P＜0.05),在海马两者差异无显著性(P＞0.05);血浆中AVP含量变化,各组间均差异无显著性(P＞0.05).相关分析:中、西药组和模型组大鼠海马AVP含量与AAR比率呈显著正相关(r=0.937,r=0.897,r=0.892;P＜0.05).结论 步长脑心通可有效改善VD大鼠学习、记忆能力,其机制之一可能与调节脑组织,尤其海马内神经递质AVP含量有关。

Clinical significance of T1-weighted MR images following transient cerebral ischemia

To try to determine the cause of hyperintensity of T1-weighted MR images that occurred on and after day 7 following transient cerebral ischemia, dynamic changes in T1-weighted images and histology of rats subjected to 20 min of 4-vessel occlusion were observed. T1-weighted images showed no remarkable alteration on days 1 and 3, although high signal intensity in the striatal region, in which the T1 value was significantly lower than the values on days 1 and 3, was observed on day 7. High signal intensity in T1-weighted images indicates low T1 values. Histological observation revealed accumulation of microglia in the striatal region on day 7 by lectin staining. There was a tight correlation between T1 values and number of lectin-positive cells. Microglia had stout processes and hypertrophic cell bodies on day 7, resembling lipid-laden phagocytes. Sudan black B staining showed the presence of many fatty droplets in the striatal region on day 7. Furthermore, double staining with lectin and Sudan black B revealed the presence of fatty droplets in bodies of lectin-positive cells on day 7. These results suggest that hyperintensity of T1-weighted images on day 7 following transient ischemia and reperfusion indicates accumulation and phagocytic activation of microglia. T1-weighted images seem to represent the progression of non-reversible tissue injury after transient ischemia and reperfusion.

One-Stage Anterior Approach for Four-Vessel Occlusion in Rat

We report a modified 4-vessel occlusion (4VO) rat model. We used a 1-stage anterior approach for making bilateral hemispheric ischemia. Modified 4VO method decreased cerebral blood flow to 12% to 14% of baseline levels. This modified 4VO method is a minimally invasive, quick, reliable procedure for producing ischemic changes.

Estrogen Restores Postischemic Sensitivity to the Thromboxane Mimetic U46619 in Rat Pial Artery

The objectives of the study were to (1) characterize the dose-response relationship to the TXA2 analog, U46619 (0.01, 0.1, and 1 micromol/L) after global cerebral ischemia, (2) determine whether chronic 17beta-estradiol (E2) replacement alters this relationship, and (3) determine if E2's mechanisms are transduced through cognate estrogen receptors. Rats were assigned to five groups (n=6): placebo-implanted ovariectomized (OVX) females, OVX plus chronic E2 (CE), OVX plus acute E2 (AE), OVX plus chronic E2 plus the estrogen receptor inhibitor ICI 182,780 (CEI), and OVX plus acute E2 plus ICI 182,780 (AEI). Rats were anesthetized, intubated, cannulated (femoral artery and vein), fitted with a closed cranial window, and subjected to 15-min reversible forebrain ischemia (4-vessel occlusion, 4-VO) and 60 mins of reperfusion. Arterial blood gases, intrawindow pressure, and temperature were controlled. Vessel diameter was measured before and 5 mins after superfusion of each concentration of U46619. Compared with preischemic responses, contractile response to U46619 was depressed at all concentrations after ischemia in the OVX group. In the chronic E2 and acute E2 groups, contractile response to 1 micromol/L of U46619 was normalized to near baseline values. However, in the CEI and the AEI groups, postischemic vasoconstriction was similar to that observed in the OVX rats. We conclude that E2 targets the cerebral microvasculature to preserve postischemic pial artery reactivity and that the effect is receptor mediated. Restoration of normal constriction to vascular agonists may be an important mechanism by which E2 protects the vasculature and diminishes tissue damage after ischemia.

Protective Preconditioning by Transient Global Ischemia in the Rat: Components of Delayed Injury Progression and Lasting Protection Distinguished by Comparisons of Depolarization Thresholds for Cell Loss at Long Survival Times

Robust ischemic preconditioning has been shown in rodent brain, but there are concerns regarding the persistence of neuron protection. This issue was examined in rat hippocampus following 4-vessel occlusion (4-VO) ischemia, using DC shifts characteristic of ischemic depolarization to reproducibly define insult severity. Preconditioning ischemia producing 2 to 3.5 mins depolarization was followed at intervals of 2, 5, or 7 days by test insults of varied duration, after which CA1 counts were obtained at 1, 2, 4, or 12 weeks. Neuron loss in naive animals increased with depolarization time longer than 4 mins regardless of postischemic survival interval. Preconditioning 2, 5, or 7 days before test insults prolonged the injury threshold evaluated at 1 week survival to 15, 9, or 6 mins, respectively, showing robust protection and a rapid decay of the protected state. However, by 2 weeks survival after preconditioning at a 2-day interval, the injury threshold dramatically regressed from 15 to 9 mins. Thereafter protection remained relatively stable through 1 month, but slight progression of neuron injury was evident at 3 months. Inflammatory responses were seen in both naive and preconditioned hippocampi throughout this interval, appropriate to the extent of neuron injury. These studies show distinct components of transient and lasting protection after ischemic preconditioning. Finally, it was found that ischemic depolarization was delayed by approximately 1 min in optimally preconditioned rat hippocampus, in contrast to previous results in the gerbil, identifying one specific mechanism by which insult severity is reduced in this model.

Neuroprotection against ischemic CA1 neurodegeneration by pituitary adenylate cyclase activating polypeptide via cAMP-response-element-binding protein-mediated enhancement of endogenous DNA repair

Emerging evidence suggests that accumulation of oxidative DNA damage in nuclear genome is an important contributing factor in neuronal cell death after cerebral ischemia. It has been shown in various models of cerebral ischemia/reperfusion that there is accumulation of oxidative DNA base damage and apurinic/apyridinic abasic site (AP site) in injured neurons, which could mediate neuronal degeneration by triggering various pro-apoptotic molecules. In the brain most types of oxidative DNA damage are repaired via the base-excision repair (BER) pathway that is highly inducible in response to various sublethal stimuli. Thus, interventions that enhance the activity of the BER pathway may be a potential therapeutic strategy against ischemic cell death. In the present study, we have examined the neuroprotective effect of the neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) in the rat model of transient global cerebral ischemia. Further, we have investigated the role of BER regulation as a potential mechanism underlying the effect of PACAP. PACAP, when infused intracerebroventricularly in the rat, potently protected against CA1 neuronal cell death after global cerebral ischemia produced by 12 minutes of 4-vessel occlusion. Associated with this neuroprotection, PACAP treatment reduced the accumulation of oxidative DNA lesions, especially AP site, and subsequently attenuated the activation of pro-apoptotic molecules p53 and PUMA in the CA1 sector, suggesting that the effect of PACAP may involve the acceleration of the repair process of endogenous oxidative DNA damage. To investigate the underlying mechanism, cellular BER activity and the expression of BER enzymes were measured in the hippocampal extracts. The results revealed that PACAP markedly enhanced the hippocampal expression (at both mRNA and protein levels) and activities of the essential BER enzymes AP endonuclase (APE) and DNA polymerase-beta. Furthermore, based on the results of inhibition studies, the inducible effect of PACAP on the BER pathway was found to be dependent on the phosphorylation and nuclear translocation of cAMP-response-element-binding protein (CREB), which mediated the enhanced transcription of both APE and DNA polymerase-beta. Finally, the effect of PACAP on BER and neuroprotection was mimicked by the administration of a cAMP/protein kinase A (PKA) agonist. The results of the present study demonstrate the neuroprotective effect of PACAP in hippocampal CA1 neurons after transient global cerebral ischemia. The effect of PACAP is dependent on the activation and nuclear translocation of CREB, and involves CREB-mediated activation of BER pathway for endogenous DNA repair. The results suggest that enhancement of neuronal DNA repair capacity by PACAP or other means may be a novel potential therapeutic approach to limit ischemic neuronal loss. (This project was supported by NIH grants NS36736, NS38560, NS 43802, and NS45048).

Inhibition of Vascular Nitric Oxide after Rat Chronic Brain Hypoperfusion: Spatial Memory and Immunocytochemical Changes

An aging rat model of chronic brain hypoperfusion (CBH) that mimics human mild cognitive impairment (MCI) was used to examine the role of nitric oxide synthase (NOS) isoforms on spatial memory function. Rats with CBH underwent bilateral common carotid artery occlusion (2-vessel occlusion (2-VO)) for either 26 or 8 weeks and were compared with nonoccluded sham controls (S-VO). The neuronal and endothelial (nNOS/eNOS) constitutive inhibitor nitro-L-arginine methyl ester (L-NAME) 20 mg/kg was administered after 26 weeks for 3 days to 2-VO and S-VO groups and spatial memory was assessed with a modified Morris watermaze test. Only 2-VO rats worsened their spatial memory ability after L-NAME. Electron microscopic immunocytochemical examination using an antibody against eNOS showed 2-VO rats had significant loss or absence of eNOS-containing positive gold particles in hippocampal endothelium and these changes were associated with endothelial cell compression, mitochondrial damage and heavy amyloid deposition in hippocampal capillaries and perivascular region. In the 8-week study, three groups of 2-VO rats were administered an acute dose of 7-NI, aminoguanidine or L-NIO, the relatively selective inhibitors of nNOS, inducible NOS and eNOS. Only rats administered the eNOS inhibitor L-NIO worsened markedly their watermaze performance (P = 0.009) when compared with S-VO nonoccluded controls. We conclude from these findings that vascular nitric oxide derived from eNOS may play a critical role in spatial memory function during CBH possibly by keeping cerebral perfusion optimal through its regulation of microvessel tone and cerebral blood flow and that disruption of this mechanism can result in spatial memory impairment. These findings may identify therapeutic targets for preventing MCI and treating Alzheimer's disease.

Temporal effects of edaravone, a free radical scavenger, on transient ischemia-induced neuronal dysfunction in the rat hippocampus

We examined the effect of a free radical scavenger edaravone on ischemia/reperfusion-induced impairment of long-term potentiation in the perforant path-dentate gyrus synapses of the rat hippocampus, as a measure of functional outcome 4 days after transient global ischemia (2-vessel occlusion, 10 min). Edaravone (3 and 10 mg/kg, i.v.) immediately after reperfusion (Day 0) alleviated ischemia-induced impairment of long-term potentiation in a dose-related manner, whereas treatment on Day 1 or 4 after reperfusion failed to rescue the impaired long-term potentiation. Edaravone administration on Day 0 also prevented the post-ischemic increase in hydroxyl radical formation and the expression of vascular endothelial growth factor, basic fibroblast growth factor and neuronal and inducible nitric oxide synthases of the hippocampus. Thus, edaravone protected the rat hippocampus from ischemia-induced long-term potentiation impairment with a therapeutic time window, suggesting that free radical formation after ischemia/reperfusion is a pivotal trigger of neurofunctional complications after global ischemic stroke.

Permanent, 3-stage, 4-vessel occlusion as a model of chronic and progressive brain hypoperfusion in rats: a neurohistological and behavioral analysis

Permanent, 3-stage, 4-vessel occlusion (4-VO) was evaluated as a practicable model of progressive, cerebral hypoperfusion in rats, resulting in quantifiable, reproducible, neuronal damage within a time interval shorter than that described in the 2-VO model. The effect of permanent and graded 4-VO on cognition was also evaluated using the newly developed, aversive radial maze. The vertebral arteries (VA) plus the common carotid arteries (CCA) or internal carotid arteries (ICA) were progressively and permanently occluded, following different experimental sequences (CCA → VA; VA → CCA → CCA or VA → ICA → ICA) with inter-stage intervals ranging from 1 to 4 weeks. Only two of four groups subjected to 2-stage 4-VO (CCA → VA) showed modest reduction in the number of normal-appearing CA1 pyramidal cells, despite the significant treatment effect ( p < 0.001–0.01 versus sham). A high rate of mortality (63.8%) was associated with 2-stage 4-VO. More pronounced and consistent neuronal damage occurred 8 weeks after 3-stage 4-VO, following the sequence VA → CCA → CCA ( p < 0.001). One month after this schedule, profound, persistent cognitive impairment was demonstrated in the aversive radial maze ( p < 0.01–0.0001). This behavioral effect was not manifested when the ICA, rather than the CCA, were occluded, despite the presence of significant, although less severe, hippocampal lesioning. The mortality rate was significantly reduced when 3-stage 4-VO was used ( p < 0.0001). These consistent, histological and behavioral effects, combined with a low mortality rate, suggest that permanent, 3-stage 4-VO may represent a reliable animal model of chronic, progressive, cerebral hypoperfusion.

Reproducible loss of CA1 neurons following carotid artery occlusion combined with halothane-induced hypotension

The 2-vessel occlusion approach to produce global ischemia in rats requires concomitant reduction of systemic blood pressure. We have utilized the hypotensive effect of halothane administrated by artificial respiration to prevent respiratory arrest and to ensure stable physiological conditions. Systemic blood pressure was reduced to 40–45 mm Hg by instant adjustments of the halothane concentration. Bilateral occlusion of the carotid arteries caused a profound and reproducible ischemia, as analyzed by laser-Doppler flowmetry. In the rats exposed to 11, 12, or 13 min of ischemia, 5% died and 5% developed seizures. The extent of neuronal death in CA1 was highly correlated to the duration of ischemia. Following 11 min of ischemia, CA1 neuronal cell death, as analyzed by Fluoro-Jade, was absent 1 day after injury, variable at day 4, and consistent at day 7. The numbers of cresyl violet- and NeuN-positive neurons at day 7 were 8% and 20% of control, respectively. OX42 immunoreactivity was low and variable at day 4, but pronounced at day 7. In conclusion, this rat global ischemia model is relatively simple to perform, has a low mortality, and produces a profound and highly reproducible delayed cell death of hippocampal CA1 neurons.

Dentate Gyrus Neurogenesis after Cerebral Ischemia and Behavioral Training

Neurogenesis in the mammalian brain continues throughout adulthood. Several factors have been shown to influence neurogenesis, including experience in a complex environment (EC), exercise (EX), and ischemic insult. The authors investigated the effects of behavioral rehabilitation training following transient global cerebral ischemia on the number of new cells in the dentate gyrus that incorporated bromodeoxyuridine (BrdU), a thymidine analog that labels cells undergoing DNA replication. Seventy-two animals were included in the study, and 4-vessel occlusion was used to induce cerebral ischemia while control animals were subjected to anesthesia and sham surgery alone. Within 3 days of surgery, rats were randomly assigned to either EC, EX, or control (paired housing in standard laboratory conditions) groups. All animals were sacrificed 2 weeks after behavioral training. Immunohistochemistry results showed an increased number of BrdU-labeled cells in the subgranular zone of the dentate gyrus in all ischemic groups and in the EC and EX sham groups, although no significant group differences were seen. Examination of cell phenotype showed that almost all BrdU-positive cells colabeled with TuJ1, an immature neuron marker, in all animals whereas only a few BrdU-positive cells colabeled with NeuN, a mature neuron marker. BrdU/NeuN-labeled cells were seen only in the sham and ischemia EC groups. No new cells showed glial fibrillary acidic protein, astrocyte marker, colabeling. These results suggest that the adult brain has an inherent regenerative capacity after insult and that behavioral training following injury does not have an additive effect on neurogenesis. Finally, the enhanced maturation of BrdU-positive cells seen in the EC rats is probably modulated by environmental cues.

Depolarization thresholds for hippocampal damage, ischemic preconditioning, and changes in gene expression after global ischemia in the rat

Induced ischemic tolerance in rat hippocampus was investigated in a forebrain ischemia model of repeated 4-vessel occlusion (4-VO). Ischemic insult variability was reduced by the use of dc potential measurements to determine the duration of ischemic depolarization in hippocampus. The results demonstrate a depolarization threshold for ischemic injury to CA1 neurons of 4–6 min and a window for optimal preconditioning of 2.5–3.5 min. Levels of induced mRNAs encoding hsp72 and several immediate-early genes were also shown to vary with depolarization interval. Immediate-early genes were maximally induced after depolarization periods inducing optimal preconditioning, while hsp72 expression increased with insult severity over the range leading to neuron loss. These results are similar to those obtained in gerbil studies indicating that preconditioning does not require large increases in hsp72 expression, and demonstrate the fundamental comparability of rodent global ischemia models when monitored by this approach.

Effect of electroacupuncture on expression of p53 protein in cerebral cortex of rats with global cerebral ischemia/reperfusion injury

Objective: To observe the effect of electroacupuncture (EA) on expression of p53 protein in cerebral cortex of senile rats with global cerebral ischemia/reperfusion (IR) injury and to explore its mechanism.Methods: The cerebral IR injury rat model was established referring to Pulsinelli 4-vessel occlusion method. Thirty-six SD rats were randomly and evenly divided into the control group, the IR group and the IR plus EA (IR-EA) group. The animals in the control group were subjected to electrocauterization of vertebral arteries in bilateral flank orifice alone with the general carotid arteries unoccluded. To rats in the IR-EA group, immediately and 24h, 48h, 72h after cerebral IR, EA treatment on bilateral acupoint “Zusanli” (ST36) was applied once a day, lasting for 60 minutes. After the final treatment, all the rats were sacrificed and their brains were taken to examine p53 protein expression by the immunohistochemical method.Results: Cells with positive p53 immunoreactivity in the cerebral cortex of rats in the IR group was significantly higher than that in the control group (P<0.05), while that in the IR-EA group was significantly lower than that in the IR group (P<0.05).Conclusion: EA could remarkably reduce expression of p53 protein in the cerebral cortex of senile rats with global cerebral IR injury, which might be one of the means for EA to inhibit neuronal apoptosis after cerebral IR injury.

An S-Nitrosylated Hemoglobin Derivative Protects the Rat Hippocampus From Ischemia-Induced Long-Term Potentiation Impairment With a Time Window

Evidence suggests that S-nitrosylation is a biological process involved in cerebral ischemia. The aim of the present study was to elucidate the effects of S-nitrosylated (SNO) polyethylene glycol-conjugated (PEG) hemoglobin (Hb) developed as an artificial oxygen carrier, which can absorb free NO and translocate NO to a sulfhydryl (SH) moiety, on ischemic cerebral dysfunction. Long-term potentiation (LTP) in the perforant path-dentate gyrus synapses of the rat hippocampus was evaluated as functional outcome 4 days after transient incomplete cerebral ischemia (2-vessel occlusion: 2VO, 10 min). SNO-PEG-Hb (250 mg/kg, i.v.) administered on Day 0, 1, 2, or 4 (immediately, 24 h, 48 h, or 96 h after reperfusion, respectively) alleviated 2VO-induced LTP impairment with a therapeutic time window. The effect was significant when SNO-PEG-Hb was administered on Day 1 or 2. SNO-PEG-Hb altered NOS features observed in the vehicle-treated 2VO rat, upregulation of eNOS, nNOS, and iNOS expressions at mRNA and protein levels; SNO-PEG-Hb further upregulated eNOS and nNOS and downregulated iNOS expressions. These findings suggest that SNO-PEG-Hb might have protective effects on the rat hippocampus from ischemia/reperfusion-induced functional damages, thereby increasing the therapeutic potential as an artificial oxygen carrier for use in the area of oxygen therapy.

Nitric oxide-mediated protection by s-nitroso-polyethylene glycol-conjugated hemoglobin of brain damage after transient cerebral ischemia/reperfusion in a rat 2-vessel occlusion model

Nitric oxide-mediated protection by s-nitroso-polyethylene glycol-conjugated hemoglobin of brain damage after transient cerebral ischemia/reperfusion in a rat 2-vessel occlusion model

Tacrolimus (FK506) reduces ischemia-induced hippocampal damage in rats: a 7- and 30-day study.

The neuroprotective effect of the immunosuppressant agent FK506 was evaluated in rats after brain ischemia induced for 15 min in the 4-vessel occlusion model. In the first experimental series, single doses of 1.0, 3.0 or 6.0 mg FK506/kg were given intravenously (iv) immediately after ischemia. In the second series, FK506 (1.0 mg/kg) was given iv at the beginning of reperfusion, followed by doses applied intraperitoneally (ip) 6, 24, 48, and 72 h post-ischemia. The same protocol was used in the third series except that all 5 doses were given iv. Damage to the hippocampal field CA1 was assessed 7 or 30 days post-ischemia on three different stereotaxic planes along the septotemporal axis of the hippocampus. Ischemia caused marked neurodegeneration on all planes (P<0.001). FK506 failed to provide neuroprotection to CA1 both when applied iv as a single dose of 1.0, 3.0 or 6.0 mg/kg (experiment 1), and after five iv injections of 1.0 mg/kg (experiment 3). In contrast, the repeated administration of FK506 combining iv plus ip administration reduced CA1 cell death on all stereotaxic planes both 7 and 30 days post-ischemia (experiment 2; P<=0.01). Compared to vehicle alone, FK506 reduced rectal temperature in a dose-dependent manner (P<=0.05); however, this effect did not alter normothermia (37 C). FK506 reduced ischemic brain damage, an effect sustained over time and apparently dependent on repeated doses and on delivery route. The present data extend previous findings on the rat 4-vessel occlusion model, further supporting the possible use of FK506 in the treatment of ischemic brain damage.

Effects of ibudilast on hippocampal long-term potentiation and passive avoidance responses in rats with transient cerebral ischemia

The present study evaluated the effects of ibudilast on impaired passive avoidance responses and hippocampal long-term potentiation (LTP) caused by transient cerebral ischemia in rats. The hippocampal nerve cell density was also measured. The latency determined in retention trials of passive avoidance shortened significantly in the 4-vessel occlusion (4VO) group (in which four blood vessels were occluded for 20 min to cause cerebral ischemia). A significant recovery in the latency was observed by administration of ibudilast (10 mg kg −1). The population spike amplitude in both the hippocampal CA1 region and perforant path-dentate gyrus synapses was potentiated by tetanus stimulation in the sham-operated group, while in the 4VO group, LTP was significantly inhibited. This inhibition was reversed by administration of ibudilast (10 mg kg −1). A marked reduction of cell densities in the CA1 region was observed in the 4VO group compared with the normal group. The nerve cell density in the hippocampal CA1 region was decreased by 20 min of cerebral ischemia. Ibudilast significantly inhibited the reduction of cell densities in a dose-dependent manner. In contrast, the cell density in the dentate gyrus was comparable in the 4VO and normal groups, and no significant changes were observed in the ibudilast groups. These findings suggest that ibudilast might possess neuronally protective properties, i.e. protecting neurons not only from deaths but also from functional damage due to certain cerebral ischemia.

Neuroprotection by methanol extract of Uncaria rhynchophylla against global cerebral ischemia in rats

In traditional Oriental medicine, Uncaria rhynchophylla has been used to lower blood pressure and to relieve various neurological symptoms. However, scientific evidence related to its effectiveness or precise modes of action has not been available. Thus, in the current study, we evaluated neuroprotective effects of U. rhynchophylla after transient global ischemia using 4-vessel occlusion model in rats. Methanol extract of U. rhynchophylla administered intraperitoneally (100–1000 mg/kg at 0 and 90 min after reperfusion) significantly protected hippocampal CA1 neurons against 10 min transient forebrain ischemia. Measurement of neuronal cell density in CA1 region at 7 days after ischemia by Nissl staining revealed more than 70% protection in U. rhynchophylla-treated rats compared to saline-treated animals. In U. rhynchophylla-treated animals, induction of cyclooxygenase-2 in hippocampus at 24 hr after ischemia was significantly inhibited at both mRNA and protein levels. Furthermore, U. rhynchophylla extract inhibited TNF-α and nitric oxide production in BV-2 mouse microglial cells in vitro. These anti-inflammatory actions of U. rhynchophylla extract may contribute to its neuroprotective effects.

Management of the carotid artery at the skull base

Purpose: To determine appropriate management of benign lesions with significant involvement of the carotid artery at the skull base and present an algorithm for safe treatment of these patients. Materials and Methods: From 1982 to 1999, 115 patients with significant parapharyngeal space masses were treated at our institution. Of these patients, 43 had lesions involving the carotid artery at the skull base and served as the basis for this study. All patients underwent preoperative computed tomography or magnetic resonance imaging scans to determine carotid involvement, and all had preoperative 4-vessel arteriograms and carotid occlusion tests with continuous electroencephalography or neurologic examination monitoring to predict safety of carotid sacrifice. Results: Of 43 patients, 41 passed carotid occlusion testing and were treated surgically. Of these patients, 33 (81%) underwent resection of their lesions with preservation of the internal carotid artery, 5 (12%) had resection with bypass or reconstruction of the artery, and 3 (7%) had en bloc resections without artery reconstruction. There were no transient or permanent neurologic sequelae in any patient. Conclusions: When carotid artery encasement occurs in the setting of benign lesions at the skull base, safe resection with vascular preservation is possible in most cases. If carotid artery resection is necessary, vascular bypass or reconstruction is recommended to minimize neurologic morbidity. (Am J Otolaryngol 2001;22:336-342. Copyright © 2001 by W.B. Saunders Company)

Cytoprotective effect of Scutellaria baicalensis in CA1 hippocampal neurons of rats after global cerebral ischemia

Based on the use of Scutellaria baicalensis for the treatment of stroke in traditional Oriental medicine, the current study was carried out to evaluate neuroprotective effects of S. baicalensis after transient global ischemia using rat 4-vessel occlusion model. Methanol extracts from the dried roots of S. baicalensis (0.1–10 mg/kg) administered intra-peritoneally significantly protected CA1 neurons against 10 min transient forebrain ischemia as demonstrated by measuring the density of neuronal cells stained with Cresyl violet. Methanol extract of S. baicalensis inhibited microglial tumor necrosis factor-alpha (TNF-α) and nitric oxide production, and protected PC12 cells from hydrogen peroxide-induced toxicity in vitro.