Anesthesia care in the interventional neuroradiology suite: an update.

PURPOSE OF REVIEW: The scope of procedures conducted by neurointerventionalists is expanding quickly, with lacking consensus over the best anesthesia modality. Although the procedures involve all age groups, the interventions may be complex and lengthy and may be provided in hospitals currently not yet familiar with the field. Here we review current literature addressing elective outpatient neurointerventional procedures and aim to provide an update on the management of intervention-specific crises, address special patient populations, and provide key learning points for everyday use in the neurointerventional radiology suite. RECENT FINDINGS: Various studies have compared the use of different anesthesia modalities and preinterventional and postinterventional care. Monitored anesthesia care is generally recommended for elderly patients, whereas children are preferably treated with general anesthesia. Additional local anesthesia is beneficial for procedures, such as percutaneous kyphoplasty and vascular access. SUMMARY: Combining different anesthetic modalities is a valuable approach in the neurointerventional radiology suite. More interventional and patient population-specific studies are needed to improve evidence-based perioperative management.

Protective role of fingolimod (FTY720) in rats subjected to subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a neurological emergency with limited pharmacological treatment options. Inflammation is increasingly recognized as a key pathogenic contributor to brain injury in this condition. In the present study, we examined the neuroprotective effects of the immunomodulatory agent, fingolimod, in rats subjected to SAH. METHODS: We utilized an endovascular rat perforation model of SAH. Animals were divided into four groups: (1) sham-vehicle; (2) sham-fingolimod; (3) SAH-vehicle; and (4) SAH-fingolimod. Rats received either vehicle solution or fingolimod (0.5 mg/kg) intraperitoneally 3 hours after sham surgery or SAH. A closed cranial window and intravital microscope system was used at 48 hours to assess neuroinflammation, which was represented by rhodamine-6G-labeled leukocyte trafficking in pial venules, and pial arteriolar dilating responses to a variety of vasodilators, including hypercapnia, and topically-applied acetylcholine, adenosine, and S-nitroso-N-acetyl penicillamine. In addition, motor-sensory function was evaluated. RESULTS: Compared to sham-vehicle rats, SAH-vehicle animals displayed a four-times greater increase in pial venular intraluminal leukocyte adhesion. Treatment with fingolimod largely reduced the intravascular leukocyte adhesion. Vehicle-treated SAH animals displayed a significant decrease in pial arteriolar responses to all the vasodilators tested and vascular reactivity was preserved, to a significant degree, in the presence of fingolimod. In addition, neurological scores obtained at 48 hours post-SAH indicated significant neurological deficits in the vehicle-treated group (versus sham-vehicle surgical control). Those deficiencies were partially reduced by fingolimod (P < 0.0001 compared to the vehicle-treated SAH group). CONCLUSIONS: Treatment of rats with fingolimod was associated with a marked limitation in the intravascular adhesion of leukocytes to pial venules, preserved pial arteriolar dilating function, and improved neurological outcome in rats subjected to SAH.

Post-ischemic vascular adhesion protein-1 inhibition provides neuroprotection in a rat temporary middle cerebral artery occlusion model.

We examined the neuroprotective efficacy associated with post-ischemic vascular adhesion protein-1 (VAP-1) blockade in rats subjected to transient (1 h) middle cerebral artery occlusion (MCAo). We compared saline-treated control rats to rats treated with a highly selective VAP-1 inhibitor, LJP-1586 [Z-3-fluoro-2-(4-methoxybenzyl) allylamine hydrochloride]. Initial intraperitoneal LJP-1586 (or saline control) treatments were delayed until 6 h or 12 h reperfusion. At 72-h reperfusion, LJP-1586-treated rats displayed 51% and 33% smaller infarct volumes, relative to their controls, in the 6- and 12-h treatment groups, respectively. However, only in the 6-h treatment group was the infarct volume reduction significant (p < 0.05). On the other hand, we observed significantly improved neurologic functions in both 6- and 12-h treatment groups, versus their matched controls (p < 0.05). Also, the effect of 6-h LJP-1586 treatment on post-ischemic leukocyte trafficking in pial venules overlying the ischemic cortex was evaluated using intravital microscopy. These experiments revealed that: 1) LJP-1586 did not affect intravascular leukocyte (largely neutrophil) adhesion, at least out to 12-h reperfusion; and 2) the onset of neutrophil extravasation, which occurred between 6-8-h reperfusion in control rats, was prevented by LJP-1586-treatment. In conclusion, in rats subjected to transient MCAo, selective VAP-1 pharmacologic blockade provided neuroprotection, with a prolonged therapeutic window of 6-12-h reperfusion.

Impairment of neurovascular coupling in type 1 diabetes mellitus in rats is linked to PKC modulation of BK(Ca) and Kir channels.

We hypothesized that chronic hyperglycemia has a detrimental effect on neurovascular coupling in the brain and that this may be linked to protein kinase C (PKC)-mediated phosphorylation. Therefore, in a rat model of streptozotocin-induced chronic type 1 diabetes mellitus (T1DM), and in nondiabetic (ND) controls, we monitored pial arteriole diameter changes during sciatic nerve stimulation and topical applications of the large-conductance Ca(2+)-operated K(+) channel (BK(Ca)) opener, NS-1619, or the K(+) inward rectifier (Kir) channel agonist, K(+). In the T1DM vs. ND rats, the dilatory response associated with sciatic nerve stimulation was decreased by ∼30%, whereas pial arteriolar dilations to NS-1619 and K(+) were largely suppressed. These responses were completely restored by the acute topical application of a PKC antagonist, calphostin C. Moreover, the suffusion of a PKC activator, phorbol 12,13-dibutyrate, in ND rats was able to reproduce the vascular reactivity impairments found in T1DM rats. Assay of PKC activity in brain samples from T1DM vs. ND rats revealed a significant gain in activity only in specimens harvested from the pial and superficial glia limitans tissue, but not in bulk cortical gray matter. Altogether, these findings suggest that the T1DM-associated impairment of neurovascular coupling may be mechanistically linked to a readily reversible PKC-mediated depression of BK(Ca) and Kir channel activity.

Signal persistence of bispectral index and state entropy during surgical procedure under sedation.

INTRODUCTION: Bispectral index (BIS) and state entropy (SE) are prone to artifacts, especially due to electrocautery (EC). We compared the incidence of artifacts in BIS and SE during surgery under local anesthesia and sedation. METHODS: 28 females undergoing breast surgery under local anesthesia and sedation were studied. Simultaneous BIS and SE measurements were recorded every 10 seconds. Artifact was defined as a failure of the device to display a numerical value while the electrodes remained appropriately attached to the patient's forehead. Ratio of artifact to good signal was compared between BIS and SE in the presence or absence of EC use. RESULTS: 7679 data points were collected from 28 patients. Overall, artifact incidence was similar in BIS and SE (6.2% and 6.3%, resp.). In the presence of EC (1370 data points), BIS had significantly more artifact compared to SE (18.6% versus 6.4%, P < 0.0001). Without EC (6309 data points), BIS had significantly less artifact compared to SE (4.1% versus 7.3%, P < 0.0001). DISCUSSION: BIS and SE were comparable for incidence of artifacts in patients under sedation. Use of EC lead to more artifact in BIS than SE. Conversely, BIS had fewer artifacts than SE when there was no EC use.

ATP hydrolysis pathways and their contributions to pial arteriolar dilation in rats.

ATP is thought to be released to the extracellular compartment by neurons and astrocytes during neural activation. We examined whether ATP exerts its effect of promoting pial arteriolar dilation (PAD) directly or upon conversion (via ecto-nucleotidase action) to AMP and adenosine. Blockade of extracellular direct ATP to AMP conversion, with ARL-67156, significantly reduced sciatic nerve stimulation-evoked PADs by 68%. We then monitored PADs during suffusions of ATP, ADP, AMP, and adenosine in the presence and absence of the following: 1) the ecto-5'-nucleotidase inhibitor α,ß-methylene adenosine 5'-diphosphate (AOPCP), 2) the A(2) receptor blocker ZM 241385, 3) the ADP P2Y(1) receptor antagonist MRS 2179, and 4) ARL-67156. Vasodilations induced by 1 and 10 µM, but not 100 µM, ATP were markedly attenuated by ZM 241385, AOPCP, and ARL-67156. Substantial loss of reactivity to 100 µM ATP required coapplications of ZM 241385 and MRS 2179. Dilations induced by ADP were blocked by MRS 2179 but were not affected by either ZM 241385 or AOPCP. AMP-elicited dilation was partially inhibited by AOPCP and completely abolished by ZM 241385. Collectively, these and previous results indicate that extracellular ATP-derived adenosine and AMP, via A(2) receptors, play key roles in neural activation-evoked PAD. However, at high extracellular ATP levels, some conversion to ADP may occur and contribute to PAD through P2Y(1) activation.

Assessment of Anesthesia Practice Patterns for Endovascular Therapy for Acute Ischemic Stroke: A Society for Neuroscience in Anesthesiology and Critical Care (SNACC) Member Survey.

BACKGROUND: The choice of general anesthesia (GA) or conscious sedation (CS) may impact neurological outcomes of patients undergoing endovascular therapy (EVT) for acute ischemic stroke (AIS). The aim of this survey was to describe the practice patterns of members of the Society for Neuroscience in Anesthesiology and Critical Care (SNACC) for anesthetic management of AIS. METHODS: Following institutional review board approval, a 16-question online survey assessing anesthetic management of patients with AIS undergoing EVT was circulated to members of SNACC. RESULTS: A total of 76 SNACC members from 52 institutions and 11 countries completed the survey (12.5% response rate). Overall, 33% of institutions reported dedicated neuroanesthesia teams for EVT. Patients treated with GA ranged from 5% to 100% between centers. In total 51% and 49% of centers in the United States reported preferentially providing GA and CS, respectively, compared with 34% and 66%, respectively, in European centers. Reported anesthetic induction agents are propofol (64%), etomidate (4%) and either medication (33%). For maintenance of GA, volatile anesthetic is used more often (54%) than propofol (16%). There was wide variation in medications used for CS. Arterial catheter placement was reported by 75% and 43% of respondents for patients undergoing GA and CS, respectively. Systolic blood pressure >140 mm Hg was targeted by 35.7% of respondents, with others targeting mean arterial pressure within 10%, 20% or 30% of baseline values. Phenylephrine and norepinephrine were the most commonly used vasopressors. CONCLUSIONS: There is wide variation in anesthesia technique and hemodynamic management during EVT for AIS, and no consensus on the choice of, or preferred medications for, GA or CS, or target blood pressure and management of hypotension during the procedure.

Subarachnoid hemorrhage in C57BL/6J mice increases motor stereotypies and compulsive-like behaviors.

OBJECTIVE: Long-term behavioral, mood, and cognitive deficits affect over 30% of patients with subarachnoid hemorrhage (SAH). The aim of the present study was to examine the neurobehavioral outcomes following endovascular perforation induced SAH in mice. METHODS: C57BL/6 J (B6) mice were exposed to endovascular perforation induced SAH or control surgery. Three weeks later, mice received a series of behavioral tests, e.g. motor function, stereotypy, learning, memory, behavioral flexibility, depression and anxiety. The immunohistologic experiment examined neuronalloss in the cortex following SAH. RESULTS: SAH mice exhibited increased marble burying and nestlet shredding compared to that of control mice. Although SAH did not affect memory, learning or reversal learning,mice displayed greater overall object exploration in the novel object recognition test, as well as elevated perseveration during probabilistic reversal learning.In the forced swim and open field tests, SAH mice performed comparably to that of control mice. However, SAH mice exhibited an increased frequency in 'jumping' behavior in the open field test. Histological analyses revealed reduced neuron density in the parietal-entorhinal cortices of SAH mice on the injured side compared to that of control mice. DISCUSSION: The findings suggest that parietal-entorhinal damage from SAH increases stereotyped motor behaviors and 'compulsive-like' behaviors without affecting cognition (learning and memory) or mood (anxiety and depression). This model can be used to better understand the neuropathophysiology following SAH that contributes to behavioral impairments in survivors with no gross sensory-motor deficits.

Interactions between adenosine and K+ channel-related pathways in the coupling of somatosensory activation and pial arteriolar dilation.

Multiple, perhaps interactive, mechanisms participate in the linkage between increased neural activity and cerebral vasodilation. In the present study, we assessed whether neural activation-related pial arteriolar dilation (PAD) involved interactions among adenosine (Ado) A(2) receptors (A(2)Rs), large-conductance Ca(2+)-operated K(+) (BK(Ca)) channels, and inward rectifier K(+) (K(ir)) channels. In rats with closed cranial windows, we monitored sciatic nerve stimulation (SNS)-induced PAD in the absence or presence of pharmacological blockade of A(2)Rs (ZM-241385), ecto-5'-nucleotidase (α,ß-methylene-adenosine diphosphate), BK(Ca) channels (paxilline), and K(ir) channels (BaCl(2)). Individually, these interventions led to 53-66% reductions in SNS-induced PADs. Combined applications of these blockers led to little or no further repression of SNS-induced PADs, suggesting interactions among A(2)Rs and K(+) channels. In the absence of SNS, BaCl(2) blockade of K(ir) channels produced 52-80% reductions in Ado and NS-1619 (BK(Ca) channel activator)-induced PADs. In contrast, paxilline blockade of BK(Ca) channels was without effect on dilations elicited by KCl (K(ir) channel activator) and Ado suffusions, indicating that Ado- and NS-1619-associated PADs involved K(ir) channels. In addition, targeted ablation of the superficial glia limitans was associated with a selective 60-80% loss of NS-1619 responses, suggesting that the BK(Ca) channel participation (and paxilline sensitivity) derived largely from channels within the glia limitans. Additionally, blockade of either PKA or adenylyl cyclase caused markedly attenuated pial arteriolar responses to SNS and, in the absence of SNS, responses to Ado, KCl, and NS-1619. These findings suggested a key, possibly permissive, role for A(2)R-linked cAMP generation and PKA-induced K(+) channel phosphorylation in somatosensory activation-evoked PAD.

Neuroanesthesia Practice During the COVID-19 Pandemic: Recommendations From Society for Neuroscience in Anesthesiology and Critical Care (SNACC).

The pandemic of coronavirus disease 2019 (COVID-19) has several implications relevant to neuroanesthesiologists, including neurological manifestations of the disease, impact of anesthesia provision for specific neurosurgical procedures and electroconvulsive therapy, and health care provider wellness. The Society for Neuroscience in Anesthesiology and Critical Care appointed a task force to provide timely, consensus-based expert guidance for neuroanesthesiologists during the COVID-19 pandemic. The aim of this document is to provide a focused overview of COVID-19 disease relevant to neuroanesthesia practice. This consensus statement provides information on the neurological manifestations of COVID-19, advice for neuroanesthesia clinical practice during emergent neurosurgery, interventional radiology (excluding endovascular treatment of acute ischemic stroke), transnasal neurosurgery, awake craniotomy and electroconvulsive therapy, as well as information about health care provider wellness. Institutions and health care providers are encouraged to adapt these recommendations to best suit local needs, considering existing practice standards and resource availability to ensure safety of patients and providers.

Estrogen replacement therapy in diabetic ovariectomized female rats potentiates postischemic leukocyte adhesion in cerebral venules via a RAGE-related process.

In this study, we tested the hypothesis that the documented transformation of 17beta-estradiol (E2) from a counterinflammatory hormone in nondiabetic (ND) rats to a proinflammatory agent in rats with diabetes mellitus (DM) is due to an enhanced contribution from the receptor for advanced glycation end products (RAGE). Rhodamine 6G-labeled leukocytes were observed through a closed cranial window in rats. In vivo pial venular leukocyte adherence and infiltration were measured over 10 h reperfusion after transient forebrain ischemia in DM (streptozotocin) versus ND intact, ovariectomized (OVX), and E2-replaced (for 7-10 days) OVX (OVE) females. The role of RAGE was examined in two ways: 1) RAGE knockdown via topical application of RAGE antisense versus missense oligodeoxynucleotide or 2) intracerebroventricular injection of the RAGE decoy inhibitor, soluble RAGE. Among diabetic rats, the lowest levels of cortical RAGE mRNA and immunoreactivity of the RAGE ligand, AGE, were seen in OVX females, with significantly higher levels exhibited in intact and OVE females. However, results from the analysis of cortical RAGE protein only partially tracked those findings. When comparing ND to DM rats, cortical AGE immunoreactivity was significantly lower in OVE and intact females but similar in OVX rats. In DM rats, the level of postischemic leukocyte adhesion and infiltration (highest to lowest) was OVE>intact>>untreated OVX. In NDs, adhesion was highest in the untreated OVX group. Leukocyte extravasation was observed at >6 h postischemia but only in diabetic OVE and intact females and in ND OVX (untreated) rats. Pretreatment with RAGE antisense-oligodeoxynucleotide or soluble RAGE attenuated postischemic leukocyte adhesion and prevented infiltration but only in the diabetic OVE and intact groups. These results indicate that the exacerbation of postischemic leukocyte adhesion by chronic E2 replacement therapy in diabetic OVX females involves a RAGE-related mechanism. Targeting RAGE may restore the neuroprotective effect of E2 replacement therapy in diabetic females.

Effect of age on brain oxygenation regulation during changes in position.

INTRODUCTION: Reports indicate that brain regulation of oxygenation is inhibited in patients with low baseline oxyhemoglobin concentrations and that brain oxyhemoglobin concentrations are decreased with aging. The purpose of this study was to determine if regulation of brain oxygenation to changes in blood pressure is inhibited by normal aging. METHODS: Brain oxyhemoglobin (OHb) and deoxyhemoglobin (HHb) concentrations were determined from the forehead using a frequency domain near infrared spectroscopy in 27 healthy volunteers. Subjects were separated into two groups by age (20-39, n=16; 40-60, n=11). Brain hemoglobin and non-invasive blood pressure were measured in (1) supine, (2) sitting, (3) supine and (4) sitting positions with 10-min equilibration intervals between each determination. Statistical differences were determined by two way repeated measures analysis of variance. RESULTS: Young subjects were 28+/-5 years (mean+/-S.D.) and older subjects were 48+/-6 years. In supine position, OHb and HHb were 28.4+/-8.3 and 15.4+/-2.4micromol/L, respectively, in young; 22.4+/-5.7 and 13.4+/-2.9micromol/L, respectively, in older subjects, both P<0.05 between groups. Changing position from supine to sitting decreased OHb 5% and increased HHb 5% with no difference between groups. CONCLUSIONS: There was a small but significant decrease in OHb and an increase in HHb from supine to sitting position, and this effect was similar between young and older subjects. Regulation of brain oxygenation during modest decreases in blood pressure did not change in normal aging to 60 years compared to young adults.

Age effects on brain oxygenation during hypercapnia.

Previous studies showed that the cerebrovasodilation response to hypercapnia is attenuated with aging. The purpose of this study was to determine if normal aging attenuates increases in brain oxygenation during hypercapnia. Prefrontal cortex oxyhemoglobin (OHb) and deoxyhemoglobin (HHb) concentrations were measured in 13 healthy subjects ages 26 to 59 years using a frequency domain tissue oximeter. Measurements were obtained under the following conditions: (1) subject awake breathing spontaneously, (2) during mask ventilation with 21% oxygen, (3) mask ventilation with 100% oxygen, (4) 100% oxygen in a rebreathing circuit to increase end-tidal CO(2). Under baseline conditions breathing room air, there was a negative correlation between baseline OHb and age (r=-0.60, P<0.05). Ventilation with 100% oxygen increased OHb without a change in total hemoglobin and no affect of age. During mask rebreathing, end-tidal CO(2) increased from 39.5+/-5.0 mm Hg (millimeters of mercury) to 56.5+/-5.7 mm Hg, which produced significant increases in OHb and total blood volume that were negatively correlated with age (r=-0.67, P<0.05) and positively correlated to baseline OHb (r=0.60, P<0.05). These results indicate that OHb concentrations decreased with age, consistent with attenuated cerebral vasodilation during hypercapnia.

Autonomic activity during dexmedetomidine or fentanyl infusion with desflurane anesthesia.

STUDY OBJECTIVE: To evaluate autonomic activity with dexmedetomidine or fentanyl infusion and desflurane anesthesia during laparoscopic gastric banding. STUDY DESIGN: Randomized, single-blinded, open-label study. SETTING: Operating rooms at a university hospital. SUBJECTS: 40 patients scheduled for laparoscopic gastric banding with a mean body mass index of 50 kg/m2. INTERVENTIONS: Patients received either dexmedetomidine (0.5 microg/kg given intravenously over 10 minutes, 0.4 microg.kg-1.h-1, n=20) or fentanyl (0.5 microg.kg-1 bolus, 1 microg.kg-1.h-1, n=20) during anesthesia. Response entropy of the electroencephalogram was maintained at 45+/-5 by adjusting end-tidal desflurane concentration. MEASUREMENTS: In the operating room, blood pressure, heart rate (HR), response entropy, end-tidal desflurane concentration, tone entropy, and power-spectral analysis of HR were measured with the patient awake; 20, 40, and 60 minutes from intubation and the start of drug infusion; and at extubation. MAIN RESULTS: The mean end-tidal desflurane concentration during anesthesia was 4.0%+/-0.6% with dexmedetomidine and 4.1%+/-0.7% with fentanyl, indicating a similar anesthetic requirement in both groups. Autonomic activity, determined by tone entropy and spectral analysis of HR, decreased by 50% during anesthesia in both groups. The dexmedetomidine group showed a greater decrease in sympathovagal balance during anesthesia. CONCLUSION: Both dexmedetomidine and fentanyl facilitated anesthesia and attenuated autonomic activity. Dexmedetomidine produced a greater decrease in sympathovagal balance than fentanyl.

Impairment of neurovascular coupling in Type 1 Diabetes Mellitus in rats is prevented by pancreatic islet transplantation and reversed by a semi-selective PKC inhibitor.

Streptozotocin (STZ)-induced chronic hyperglycemia has a detrimental effect on neurovascular coupling, linked to increased PKC-mediated phosphorylation and PKC isoform expression changes. Here, we sought to determine whether: 1) selective PKC-α/ß/γ inhibitor, GF109203X, could reverse the effects of chronic hyperglycemia on cerebrovascular reactivity; 2) pancreatic islet transplantation could prevent the development of cerebrovascular impairment seen in a rat model of Type 1 Diabetes. We studied the effect of GF109203X in diabetic (DM), non-diabetic (ND), and transplanted (TR) Lewis rats during either sciatic nerve stimulation (SNS) or the topical applications of the large-conductance Ca2+-operated K+(BKCa) channel opener, NS1619, or the K+ inward rectifier (Kir) channel agonist, KCl. Pial arteriole diameter changes were monitored using a closed cranial window in vivo microscopy technique. The pial arteriole dilatory response associated with SNS was decreased by ~45%, when comparing DM vs either ND or TR rats. Also, pial arteriolar dilations to topical KCl and NS1619 were largely attenuated in DM rats, but not in ND or TR animals. These responses were completely restored by the acute application of GF109203X to the brain surface. The PKC inhibitor had no effect on vascular responses in normoglycemic and TR animals. In conclusion, DM-associated chronic impairment of neurovascular coupling may be readily reversed by a PKC-α/ß/γ inhibitor or prevented via pancreatic islet transplantation. We believe that specific PCK isoforms (α/ß/γ) are mechanistically linked to the neurovascular uncoupling seen with hyperglycemia.

Intracerebroventricular application of S100B selectively impairs pial arteriolar dilating function in rats.

S100B is an astrocyte-derived protein that can act through the receptor for advanced glycation endproducts (RAGE) to mediate either "trophic" or "toxic" responses. Its levels increase in many neurological conditions with associated microvascular dysregulation, such as subarachnoid hemorrhage (SAH) and traumatic brain injury. The role of S100B in the pathogenesis of microvasculopathy has not been addressed. This study was designed to examine whether S100B alters pial arteriolar vasodilating function. Rats were randomized to receive (1) artificial cerebrospinal fluid (aCSF), (2) exogenous S100B, and (3) exogenous S100B+the decoy soluble RAGE (sRAGE). S100B was infused intracerebroventricularly (icv) using an osmotic pump and its levels in the CSF were adjusted to achieve a concentration similar to what we observed in SAH. After 48 h of continuous icv infusion, a cranial window/intravital microscopy was applied to animals for evaluation of pial arteriolar dilating responses to sciatic nerve stimulation (SNS), hypercapnia, and topical suffusion of vasodilators including acetylcholine (ACh), s-nitroso-N-acetyl penicillamine (SNAP), or adenosine (ADO). Pial arteriolar dilating responses were calculated as the percentage change of arteriolar diameter in relation to baseline. The continuous S100B infusion for 48 h was associated with reduced responses to the neuronal-dependent vasodilator SNS (p<0.05) and the endothelial-dependent vasodilator ACh (p<0.05), compared to controls. The inhibitory effects of S100B were prevented by sRAGE. On the other hand, S100B did not alter the responses elicited by vascular smooth muscle cell-dependent vasodilators, namely hypercapnia, SNAP, or ADO. These findings indicate that S100B regulates neuronal and endothelial dependent cerebral arteriolar dilation and suggest that this phenomenon is mediated through RAGE-associated pathways.

VAP-1 blockade prevents subarachnoid hemorrhage-associated cerebrovascular dilating dysfunction via repression of a neutrophil recruitment-related mechanism.

Our previous findings indicated that in rats subjected to subarachnoid hemorrhage (SAH), suppression of post-SAH neuroinflammation via vascular adhesion protein-1 (VAP-1) blockade provides significant neuroprotection. We and others have reported that neuroinflammation contributes to cerebral microvascular impairment. Thus, in the present study, we tested the hypotheses that: (1) treatment with LJP-1586, a selective VAP-1 blocker, prevents SAH-associated pial arteriolar dilating dysfunction; and (2) the vasculoprotective effect of LJP-1586 arises from inhibiting SAH-elicited neutrophil recruitment. We utilized an endovascular perforation model of SAH. Rats subjected to SAH were either treated with LJP-1586 or rendered neutropenic via anti-neutrophil-antibody treatment. Findings from these groups were compared to their respective control groups. At 48 h post-SAH, rats were evaluated for neurobehavioral function, pial venular leukocyte trafficking, and pial arteriolar reactivity to topically-applied acetylcholine (ACh) and S-nitroso-N-acetyl penicillamine (SNAP). Pial arteriolar responses decreased at 48 h post-SAH. However, in the presence of LJP-1586, those responses were significantly preserved. Neutrophil-depletion yielded a substantial suppression of SAH-associated leukocyte adhesion and infiltration. This was accompanied by a significant preservation of pial arteriolar dilating function, suggesting a direct link between neutrophil recruitment and the loss of cerebral microvascular reactivity. Moreover, neutrophil depletion also was associated with significant protection of neurobehavioral function. The present findings suggest that attenuating SAH-linked elevation in neutrophil trafficking will protect against the development of microvascular dysfunction and subsequent neurological impairment.

Jet injection of local anesthetic decreases pain of arterial cannulation in awake neurosurgical patients.

Arterial cannulation through the standard skin wheal of local anesthetic raised with a needle may be painful. The authors compared the efficacy of local anesthetic injected via a 25G needle versus a Bioject jet injector for arterial cannulation in awake neurosurgical patients. After institutional review board approval, 40 patients were randomized to receive 0.3 mL 1% lidocaine adjusted to pH 7.0 with NaHCO3 by Bioject with a 2-cm spacer between the syringe and skin or by 25G needle injection. Two pain assessments were used at the time of local anesthetic injection and at arterial cannulation. Patients rated their pain on a visual analog scale (VAS) (0 = no pain, 100 = worst pain). Observers scored patient response as 0 (no response), 1 (flinch), or 2 (withdrawal). The VAS at injection was 23 +/- 19 for the needle group and 3 +/- 6 for the Bioject group (P < 0.001). The VAS at arterial cannulation was 39 +/- 25 for the needle group and 15 +/- 22 for the Bioject group (P < 0.001). Median observer scores at injection and cannulation were 1 (range 0-2) for the needle group and 0 (range 0-2) for the Bioject group (P < 0.001). Patients in the Bioject group experienced significantly less pain during lidocaine administration and at the time of arterial cannulation by their own and by an observer's assessment than the needle injection group. Jet injection of local anesthetic should be considered prior to arterial cannulation in awake patients.

Loss of SSEP during sitting craniotomy.

A 54-year-old woman with a past medical history of asthma and depression presented with right side hearing loss and ataxia. She was scheduled for a sitting craniotomy for cerebellopontine angle tumor resection. Somatosensory evoked potential, brainstem auditory evoked response, and facial nerve EMG were monitored intraoperatively. Approximately 30 minutes into the case, there was an episode of air embolism, which resolved after the source was identified and treated. Near the conclusion of the case, there was an abrupt loss of the right cortical somatosensory evoked potential signal, which never returned to baseline. A postoperative CT scan showed a substantial amount of subarachnoid air and intraventricular air in the frontal and temporal regions. The patient awakened in the ICU with no new neurologic deficit besides preoperative hearing loss on the right side. Despite the high specificity of somatosensory evoked potential change associated with postoperative neurodeficit when the change never returns to the baseline, there was no postoperative neurologic deficit in this patient. This case indicates the false-positive somatosensory evoked potentials caused by pneumocephalus in the sitting position.