Candida parapsilosis Infection of Ventriculoperitoneal Shunt in Adult: Case Report and Literature Review.

BACKGROUND: Candida parapsilosis is an incredibly rare cause of ventriculoperitoneal (VP) shunt infections, with only 1 adult case reported in the literature to date. CASE DESCRIPTION: We describe the case of a 45-year-old man admitted for a traumatic fall and subsequently treated with VP shunt placement for obstructive hydrocephalus secondary to a cerebellar contusion and intraventricular hemorrhage. Eight months following VP shunt placement, the patient presented with a 2-month history of clear fluid leakage through a dehiscent surgical abdominal wound overlying the distal VP shunt. Cerebrospinal fluid cultures were obtained and grew C. parapsilosis. The patient subsequently underwent VP shunt externalization and began antifungal treatment with intravenous liposomal amphotericin B. Cerebrospinal fluid studies continued to redemonstrate C. parapsilosis infection, for which VP shunt removal and external ventricular drain placement was performed. Three days into treatment with amphotericin B, he endured significant nephrotoxicity necessitating a switch to oral fluconazole. Following 3 weeks of oral fluconazole treatment with negative serial cerebrospinal fluid cultures, the patient underwent external ventricular drain removal and VP shunt insertion. Following the procedure and 22 total days of oral fluconazole treatment, our patient recovered well and was discharged to a rehabilitation facility in stable condition. CONCLUSIONS: In our report, we describe the clinical course of our patient and offer a review and analysis of the most up-to-date literature concerning C. parapsilosis shunt infections, as well as treatment guidelines for central nervous system candidiasis.

Laser-Assisted Excision of Coil Mass While Clipping Recurrent Intracranial Aneurysms After Prior Endovascular Coiling: Our Initial Experience.

BACKGROUND: Excision of coil mass during clipping of recurrent or residual aneurysms after prior endovascular coiling is challenging. We evaluated the use of the carbon dioxide laser for safe and effective removal of coils during aneurysm surgery. Two cases are presented. CASE DESCRIPTION: The first patient was a 56-year-old man with a previously coiled ruptured anterior communicating artery aneurysm. Angiography at 3-year follow-up showed recurrent aneurysm, which could not be coiled again owing to technical reasons. An aneurysm clip could not be safely applied owing to the weight of the coil mass compromising the parent vessel lumen. Laser-assisted coil mass resection was performed before permanent clip application. Intraoperative cerebral angiography showed complete obliteration of the aneurysm. The second patient was a 69-year-old woman with a previously coiled unruptured middle cerebral artery aneurysm. Angiography at 2-year follow-up showed recurrence of the aneurysm, which could not be coiled again owing to technical reasons. Laser-assisted coil mass resection was performed before the aneurysm was safely clipped. Intraoperative angiography showed complete obliteration of the aneurysm. No complications occurred using the carbon dioxide laser. At 1-year follow-up, both patients were asymptomatic with no evidence of aneurysmal recurrence. CONCLUSIONS: Excision of coil mass is required while treating recurrent and/or residual intracranial aneurysms that were previously treated by endovascular technique. The use of carbon dioxide laser assistance while retrieving these coils is safe and effective.

In Situ Left Azygous Anterior Cerebral Artery to Right Pericallosal Artery Bypass for Treatment of a Giant Right A1/2 Aneurysm: 2-Dimensional Operative Video.

Here we present a 46-yr-old man with recurrent syncopal episodes thought to be of cardiac origin. He was eventually found to harbor a giant, partially thrombosed, saccular aneurysm arising from the A1/A2 segment of the right anterior cerebral artery with foramen of Monro obstruction and a trapped left-sided ventricular system. An azygous left A2 artery segment supplied both callosomarginal arteries. We performed an in situ side-to-side anastomosis between the distal left azygous anterior cerebral artery and the right pericallosal artery, which was previously supplied by the right A1. The right A1 was clip ligated, and the aneurysm evacuated with an ultrasonic aspirator. Postoperatively, the patient did well with no recurrence of the aneurysm and resolution of his preoperative obstructive hydrocephalus. He continues to be independent >7 yr post surgery. His 6-mo follow-up angiogram revealed a patent bypass.

Lower airway disease and pituitary surgery: Is there an association with postoperative cerebrospinal fluid leak?

OBJECTIVES/HYPOTHESIS: To explore the relationship between lower airway disease and postoperative cerebrospinal fluid (CSF) rhinorrhea among patients undergoing pituitary surgery STUDY DESIGN: Retrospective review. METHODS: A retrospective review of the Healthcare Cost and Utilization Project's 2013 National Inpatient Sample was conducted to characterize the hospital stay and surgical outcomes of patients undergoing pituitary surgery. Patients with lower airway disease (including chronic obstructive pulmonary disease and asthma) were compared to a disease-free population identifying demographics and complications over-represented in the lower airway group. RESULTS: The majority of hypophysectomies (92.1%) were performed via a transsphenoidal approach. Among transsphenoidal patients, individuals with asthma (92.8% of the lower airway disease cohort) harbored a greater postoperative CSF leak rate (4.7% vs. 2.7%, P = .022), and were more likely to develop postoperative diabetes insipidus (6.2% vs. 4.1%, P = .024) and neurological complications (13.0% vs. 9.6%, P = .010) when compared to a lower airway disease-free cohort. Patients with CSF rhinorrhea had longer lengths of stay (7.8 days vs. 4.5 days, P < .001) and higher discharge costs ($148,309 vs. $76,246, P < .001). A binary logistic regression model identified having asthma (P = .042), being female (P = .011), and having gastroesophageal reflux disease (P = .006) as independent predictors of postoperative CSF rhinorrhea. CONCLUSIONS: Several patient comorbidities including asthma are associated with a greater risk of postoperative CSF rhinorrhea. Perioperative lower airway assessment and disease control may potentially decrease one's risk of this complication, although further inquiry is urgently needed to identify optimal preventive strategies. LEVEL OF EVIDENCE: 2c. Laryngoscope, 127:1543-1550, 2017.

Reduced Apoptosis by Ethanol and Its Association with PKC-δ and Akt Signaling in Ischemic Stroke.

Along with thrombolytic therapy, which has a number of limitations, stroke outcome may be improved with neuroprotective therapies that disrupt ischemic cell death. Recent research has shown a neuroprotective role of ethanol administration during ischemic stroke, such as its ability to reduce infarct volume and neurologic deficit. In order to investigate this further, we assessed the hypothesis that ethanol's neuroprotective effect is through reduction of apoptosis and the modulation of the important apoptotic PKC-δ and Akt signaling pathway. Ethanol (1.5 g/kg) was given by intraperitoneal injections to 54 Sprague-Dawley rats after 2 hours of middle cerebral artery (MCA) occlusion, followed by 3 or 24 hours of reperfusion. We measured apoptotic cell death, PKC-δ, and Akt mRNA and protein expressions in each of ischemic groups with or without ethanol treatment using ELISA, real-time PCR and Western blot analysis. Our results showed that cell death was significantly increased in rats following 2 hour MCA occlusion and 24 hour reperfusion. Subsequently, cell death was significantly reduced by an administration of ethanol. We further found that ethanol administration, prior to either 3 or 24 hours of reperfusion, significantly decreased the expression of PKC-δ while simultaneously increasing the expression Akt at both mRNA and protein levels at the two points. In conclusion, our study suggests that ethanol administration following ischemic stroke modulates the gene and protein profile in such a way that it increased expression of anti-apoptotic Akt and decreased the pro-apoptotic PKC-δ. This ultimately results in a decrease in neuronal apoptosis, thus conferring neuroprotection.

Reduced apoptosis by combining normobaric oxygenation with ethanol in transient ischemic stroke.

BACKGROUND AND PURPOSE: The effect of normobaric oxygen (NBO) on apoptosis remains controversial. The present study evaluated the effect of NBO on ischemia-induced apoptosis and assessed the potential for improved outcomes by combining NBO administration with another neuroprotective agent, ethanol, in a rat stroke model. METHODS: Rats were subjected to right middle cerebral artery occlusion (MCAO) for 2h. At the onset of reperfusion, ischemic animals received either NBO (2h duration), an intraperitoneal injection of ethanol (1.0g/kg), or both NBO and ethanol. Extent of brain injury was determined by infarct volume, neurological deficit, and apoptotic cell death. Expression of pro- and anti-apoptotic proteins was evaluated through Western immunoblotting. RESULTS: Given alone, NBO and ethanol each slightly (p<0.05) reduced infarct volume to 38% and 37%, respectively, as compared to the impressive reduction of 51% (p<0.01) seen with combined NBO-ethanol administration. Neurologic deficits were also significantly reduced by 48% with combined NBO-ethanol therapy, as compared to lesser reductions of 24% and 23% with NBO or ethanol, respectively. Combined NBO-ethanol therapy decreased apoptotic cell death by 49%, as compared to 31% with NBO and 30% with ethanol. Similarly, combination therapy significantly increased expression of anti-apoptotic factors (Bcl-2 and Bcl-xL) and significantly reduced expression of pro-apoptotic proteins (BAX, Caspase-3, and AIF), as compared to the minimal or nil protein expression changes elicited by NBO or ethanol alone. CONCLUSIONS: In rats subjected to ischemic stroke, NBO administration salvages ischemic brain tissue through evidenced decrease in apoptotic cell death. Combined NBO therapy with ethanol administration greatly improves both degree of neuroprotection and associated apoptosis.

Gamma Knife radiosurgery in the management of brainstem metastases.

BACKGROUND: Metastases to the brainstem portend a poor prognosis and present a challenge in clinical management. Surgical resection is rarely a viable option. METHODS: Post-treatment MRI scans of patients with brainstem metastases treated with radiosurgery were used to determine local control and disease progression. Median survival was calculated using Kaplan-Meier analysis. Univariate and multivariate analyses were performed using log-rank test and Cox proportional hazards model, respectively. RESULTS: Thirty-two consecutive patients with brainstem metastasis underwent Gamma Knife radiosurgery. Median age was 50 years. Median tumor volume was 0.71 cm3 and median tumor margin dose was 13 Gy. Seventeen of 32 patients received WBRT prior to stereotactic radiosurgery. Median survival was 5.2 months. There was a statistically significant difference in survival based on RTOG recursive partition analysis (RPA) class. Median survival of patients categorized as RPA class I was 19.2 months, RPA class II was 8.4 months, and RPA class III was 1.9 months. The overall local tumor control rate was 87.5%. There were no acute complications following stereotactic radiosurgery and no evidence of radiation necrosis noted on post-treatment MRI scans. CONCLUSION: Stereotactic radiosurgery is an effective treatment for brainstem metastases and should be considered especially for patients with good performance status.

Preischemic exercise reduces brain damage by ameliorating metabolic disorder in ischemia/reperfusion injury.

Physical exercise preconditioning is known to ameliorate stroke-induced injury. In addition to several other mechanisms, the beneficial effect of preischemic exercise following stroke is due to an upregulated capacity to maintain energy supplies. Adult male Sprague-Dawley rats were used in exercise and control groups. After 1-3 weeks of exercise, several enzymes were analyzed as a gauge of the direct effect of physical exercise on cerebral metabolism. As a measure of metabolic capacity, an ADP/ATP ratio was obtained. Glucose transporters (GLUT1 and GLUT3) were monitored to assess glucose influx, and phosphofructokinase (PFK) was measured to determine the rate of glycolysis. Hypoxia-induced factor-1α (HIF-1α) and 5'AMP-activated protein kinase (AMPK) levels were also determined. These same analyses were performed on preconditioned and control rats following an ischemic/reperfusion (I/R) insult. Our results show that GLUT1, GLUT3, PFK, AMPK, and HIF-1α were all increased following 3 weeks of exercise training. In addition, the ADP/ATP ratio was chronically elevated during these 3 weeks. After I/R injury, HIF-1α and AMPK were significantly higher in exercised rats. The ADP/ATP ratio was reduced in preconditioned rats in the acute phase after stroke, suggesting a lower level of metabolic disorder. GLUT1 and GLUT3 were also increased in the acute phase in exercise rats, indicating that these rats were better able to increase rates of metabolism immediately after ischemic injury. In addition, PFK expression was increased in exercise rats showing an enhanced glycolysis resulting from exercise preconditioning. Altogether, exercise preconditioning increased the rates of glucose metabolism, allowing a more rapid and more substantial increase in ATP production following stroke.

At low doses ethanol maintains blood-brain barrier (BBB) integrity after hypoxia and reoxygenation: a brain slice study.

Post-ischemia ethanol (EtOH) treatments have been shown to exhibit neuroprotective effects in stroke. However, the mechanisms underlying these effects and those on blood-brain barrier (BBB) integrity have yet to be elucidated. In the present study, we determined whether administering differing concentrations of EtOH alter the expressions of BBB integral proteins, including aquaporins-4 and -9 (AQP-4, AQP-9), matrix metallopeptidases-2 and -9 (MMP-2, MMP-9), zonula occludens-1 (ZO-1), and basal lamina (laminin). We employed an organotypic brain slice culture model that utilizes oxygen-glucose deprivation followed by reoxygenation (OGD/R). Brain slices were obtained from 10-day-old Sprague-Dawley rats and divided into the following five groups (n = 8 subjects per group): (1) control, (2) hypoxia (OGD/R), no EtOH, (3) OGD/R and 10 mM EtOH, (4) OGD/R and 30 mM EtOH, and (5) OGD/R and 90 mM EtOH. To assess BBB integrity, levels of AQPs, MMPs, ZO-1, and laminin were determined by Western blot. Compared to control, OGD/R without EtOH significantly increased AQP-4, AQP-9, MMP-2, and MMP-9 levels, while decreasing ZO-1 and laminin levels. All EtOH concentration treatments (groups 3 through 5) significantly reduced the expressions of AQP-4, AQP-9, MMP-2, and MMP-9, compared to the OGD/R, non-alcohol treated slices. Furthermore, compared to the OGD/R without EtOH group, the 30 mM EtOH treatment significantly increased ZO-1 and laminin levels. In contrast, the 90 mM EtOH level neither enhanced the reduction in AQP and MMP levels nor increased ZO-1 or basal lamina expressions observed in the 30 mM treatment. In conclusion, at an optimal dose of 30 mM, EtOH improves the expressions of MMP-2, MMP-9, AQP-4, AQP-9, ZO-1, and basal laminin, previously altered by OGD/R. These effects may indicate a beneficial effect of EtOH on BBB integrity after stroke.

Acute administration of ethanol reduces apoptosis following ischemic stroke in rats.

In recent studies, acute ethanol administration appears to play a neuroprotective role during ischemic stroke. We sought to confirm these findings by identifying if ethanol-derived neuroprotection is associated with a reduction in apoptosis. Ethanol at 0.5 and 1.5 g/kg doses was given by intraperitoneal injections to Sprague-Dawley rats after 2h of middle cerebral artery (MCA) occlusion, followed by reperfusion. We quantified apoptotic cell death in each of the treatment groups with ELISA, and measured pro- and anti-apoptotic protein expression with Western blot analysis. Cell death was significantly increased in rats after ischemia and was subsequently significantly reduced by the administration of 1.5 g/kg of ethanol. We found that the 1.5 g/kg dose promoted the expression of pro-survival factors and decreased the expression of apoptotic proteins at 3h after reperfusion. This effect was maintained at 24h for Caspase-3 and apoptosis-inducing factor (AIF), although not for Bcl-2, Bcl-xL, and Bcl-2-associated X (Bax). Administration of 0.5 g/kg of ethanol was not as effective in regulating protein expression as the 1.5 g/kg dose. Our study suggests that administration of ethanol at a dose of 1.5 g/kg after stroke - which provides rat blood alcohol levels equivalent to the legal driving limit - produces a differential protein profile, with increased expression of anti-apoptotic proteins and decrease in pro-apoptotic factors. This results in a significant reduction of neuronal apoptosis and is neuroprotective in ischemia-reperfusion injury.

Synergetic neuroprotection of normobaric oxygenation and ethanol in ischemic stroke through improved oxidative mechanism.

BACKGROUND AND PURPOSE: Normobaric oxygenation (NBO) and ethanol both provide neuroprotection in stroke. We evaluated the enhanced neuroprotective effect of combining these 2 treatments in a rat stroke model. METHODS: Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 hours. Reperfusion was then established and followed by treatment with either (1) an intraperitoneal injection of ethanol (1.0 g/kg), (2) NBO treatment (2-hour duration), or (3) NBO plus ethanol. The extent of brain injury was determined by infarct volume and motor performance. Oxidative metabolism was determined by ADP/ATP ratios, reactive oxygen species levels, nicotinamide adenine dinucleotide phosphate oxidase activity, and pyruvate dehydrogenase activity. Protein expression of major nicotinamide adenine dinucleotide phosphate oxidase subunits (p47(phox), gp91(phox), and p67(phox)) and the enzyme pyruvate dehydrogenase was evaluated through Western immunoblotting. RESULTS: NBO and ethanol monotherapies each demonstrated reductions as compared to stroke without treatment in infarct volume (36.7% and 37.9% vs 48.4%) and neurological deficits (score of 6.4 and 6.5 vs 8.4); however, the greatest neuroprotection (18.8% of infarct volume and 4.4 neurological deficit) was found in animals treated with combination therapy. This neuroprotection was associated with the largest reductions in ADP/ATP ratios, reactive oxygen species levels, and nicotinamide adenine dinucleotide phosphate oxidase activity, and the largest increase in pyruvate dehydrogenase activity. CONCLUSIONS: Combination therapy with NBO and ethanol enhances the neuroprotective effect produced by each therapy alone. The mechanism behind this synergistic action is related to changes in cellular metabolism after ischemia reperfusion. NBO plus ethanol is attractive for clinical study because of its ease of use, tolerability, and tremendous neuroprotective potential in stroke.

Neuroprotection conferred by post-ischemia ethanol therapy in experimental stroke: an inhibitory effect on hyperglycolysis and NADPH oxidase activation.

Ethanol provides neuroprotection following ischemia/reperfusion. This study assessed ethanol's effect on hyperglycolysis and NADPH oxidase (NOX) activation. Adult, male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h. Three sets of experiments were conducted to determine ethanol's effect on (i) conferring neuroprotection by measuring infarct volume and neurological deficits 24 h post reperfusion; (ii) cerebral glucose metabolism and lactic acidosis by measuring brain and blood glucose concentrations and protein expression of glucose transporter 1 and 3 (GLUT1, GLUT3), phosphofructokinase (PFK), as well as lactic acidosis by measuring lactate dehydrogenase (LDH), and lactate; and (iii) nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activation by detecting enzymatic activity and subunit expression at 3 h after reperfusion. When administered upon reperfusion, ethanol (1.5 g/kg) reduced infarct volume by 40% (p < 0.01) and neurological deficits by 48% at 24 h post reperfusion while reducing (p < 0.01) elevations in glycolytic protein expression and lactate levels during early reperfusion (3 h). Ethanol increased the reductions in cerebral glucose concentration at 3 h post reperfusion by 64% (p < 0.01) while enhancing (p < 0.01) post stroke blood glucose concentration, suggesting a reduced cellular glucose uptake and utilization. Ethanol decreased (p < 0.01) stroke-induced NOX activation by reducing enzymatic activity and gp91(phox) expression by 45% and 38%, respectively. Post-ischemia ethanol treatment exerts neuroprotection through attenuation of hyperglycolysis and associated NOX activation. Because of the lack of associated hypoglycemia and selectivity toward decreasing cerebral metabolism, further investigation of ethanol's use as a post-stroke therapy, especially in the context of hyperglycemia, seems warranted.

Peritumoral edema following Gamma Knife radiosurgery as the primary treatment for intraventricular meningiomas.

Intraventricular meningiomas represent a small proportion of intracranial meningiomas. Stereotactic radiosurgery (SRS) as a primary treatment for intraventricular meningiomas has been reported only recently. We present two patients with trigonal meningiomas who developed peritumoral edema 5months and 12months following SRS. The patients' inability to wean off corticosteroids and progressive worsening of neurologic symptoms required eventual microsurgical resection of the intraventricular tumors. Follow-up MRI at 3 and 4 years after surgery demonstrated no evidence of tumor recurrence. Reports of patients with ventricular meningiomas treated primarily with Gamma Knife radiosurgery are sparse. To our knowledge, this is the first report of the development of extensive peritumoral edema following SRS for intraventricular meningioma. Larger case series with longer follow-up are required to define the incidence and timing of edema formation surrounding intraventricular meningiomas following treatment with radiosurgery.

Post-operative diabetes insipidus after endoscopic transsphenoidal surgery.

Diabetes insipidus (DI) after endoscopic transsphenoidal surgery (ETSS) can lead to increased morbidity, longer hospital stays, and increased medication requirements. Predicting which patients are at high risk for developing DI can help direct services to ensure adequate care and follow-up. The objective of this study was to review our institution's experience with ETSS and determine which clinical/laboratory variables are associated with DI in this patient population. The authors wanted to see if there was an easily determined single value that would help predict which patients develop DI. This represents the largest North American series of this type. We retrospectively reviewed the charts of patients who had undergone ETSS for resection of sellar and parasellar pathology between 2006 and 2011. We examined patient and tumor characteristics and their relationship to postoperative DI. Out of 172 endoscopic transsphenoidal surgeries, there were 15 cases of transient DI (8.7%) and 14 cases of permanent DI (8.1%). Statistically significant predictors of postoperative DI (p < 0.05) included tumor volume and histopathology (Rathke's cleft cyst and craniopharyngioma). Significant indicators of development of DI were postoperative serum sodium, preoperative to postoperative change in sodium level, and urine output prior to administration of 1-deamino-8-D-arginine vasopressin. An increase in serum sodium of ≥2.5 mmol/L is a positive marker of development of DI with 80% specificity, and a postoperative serum sodium of ≥145 mmol/L is a positive indicator with 98% specificity. Identifying perioperative risk factors and objective indicators of DI after ETSS will help physicians care for patients postoperatively. In this large series, we demonstrated that there were multiple perioperative risk factors for the development of DI. These findings, which are consistent with other reports from microscopic surgical series, will help identify patients at risk for diabetes insipidus, aid in planning treatment algorithms, and increase vigilance in high risk patients.

Reduction of brain edema and expression of aquaporins with acute ethanol treatment after traumatic brain injury.

OBJECT: Previous studies have demonstrated that traumatic brain injury (TBI) causes brain edema by allowing excessive water passage through aquaporin (AQP) proteins. To establish the potential neuroprotective properties of ethanol as a post-TBI therapy, in the present study the authors determined the effect of ethanol on brain edema, AQP expression, and functional outcomes in a post-TBI setting. METHODS: Adult male Sprague-Dawley rats weighing between 425 and 475 g received a closed head TBI in which Maramarou's impact-acceleration method was used. Animals were given a subsequent intraperitoneal injection of 0.5 g/kg or 1.5 g/kg ethanol at 60 minutes post-TBI and were killed 24 hours after TBI. Brains were subsequently examined for edema along with AQP mRNA and protein expression. Additional animals treated with either 0.5 g/kg or 1.5 g/kg ethanol at 60 minutes post-TBI were designated for cognitive and motor testing for 3 weeks. RESULTS: Ethanol administration post-TBI led to significantly (p < 0.05) lower levels of brain edema as measured by brain water content. This downregulation in brain edema was associated with significantly (p < 0.05) reduced levels of AQP mRNA and protein expression as compared with TBI without treatment. These findings concur with cognitive studies in which ethanol-treated animals exhibited significantly (p < 0.05) faster radial maze completion times. Motor behavioral testing additionally demonstrated significant (p < 0.05) beneficial effects of ethanol, with treated animals displaying improved motor coordination when compared with untreated animals. CONCLUSIONS: The present findings suggest that acute ethanol administration after a TBI decreases AQP expression, which may lead to reduced cerebral edema. Ethanol-treated animals additionally showed improved cognitive and motor outcomes compared with untreated animals.

A novel technique for pedicled nasoseptal flap takedown in revision skull base surgery.

Objective To describe a novel technique of using the CO2 laser for a revision pedicled nasoseptal flap (PNSF) takedown. Patient Patient with a pituitary adenoma recurrence that had undergone an endoscopic skull base resection with a nasoseptal flap repair 3 years prior. Procedure Flap edges and bony defect are examined using an image-guidance probe to identify the full extent of the defect. The CO2 laser fiber is used to incise through to the underlying skull base. The flap is then elevated from its most distal portion toward the pedicle, using the laser to cut adhesions away from the underlying dura. The skull base defect is then repaired with an onlay graft of acellular dermis, then the PNSF. Results The laser was adept at dissecting through mucosa to the underlying bone and at dissecting the underside of the flap from the posterior adhesions and intradural structures safely. Conclusion The novel use of the of the CO2 laser for the flap takedown was very effective at safely making the mucosal cuts and dissecting the flap from the underlying structures. The nasoseptal flap takedown can be a technically challenging procedure that was made easier by the use of the CO2 laser.

Neuronal damage and functional deficits are ameliorated by inhibition of aquaporin and HIF1α after traumatic brain injury (TBI).

The present study, using a rodent model of closed-head diffuse traumatic brain injury (TBI), investigated the role of dysregulated aquaporins (AQP) 4 and 9, as well as hypoxia inducible factor -1α(HIF-1α) on brain edema formation, neuronal injury, and functional deficits. TBI was induced in adult (400-425 g), male Sprague-Dawley rats using a modified Marmarou's head impact-acceleration device (450 g weight dropped from 2m height). Animals in each treatment group were administered intravenous anti-AQP4 or -AQP9 antibodies or 2-Methoxyestradiol (2ME2, an inhibitor of HIF-1α) 30 min after injury. At 24h post-TBI, animals (n=6 each group) were sacrificed to examine the extent of brain edema by water content, as well as protein expression of AQP and HIF-1α by Western immune-blotting. At 48-hours post-TBI, neuronal injury (n=8 each group) was assessed by FluoroJade (FJ) histochemistry. Spatial learning and memory deficits were evaluated by radial arm maze (n=8 each group) up to 21 days post-TBI. Compared to non-injured controls, significant (p<0.05) increases in the expression of AQP4 and -9 were detected in the brains of injured animals. In addition, significant (p<0.05) brain edema after TBI was associated with increases (p <0.05) both in neuronal injury (FJ labeling) and neurobehavioral deficits. Selective inhibition of either AQP4 or -9, or HIF-1α significantly (p<0.05) decreased the expression of the proteins. In addition, inhibition of the AQPs and HIF-1α significantly (p<0.05) ameliorated brain edema, as well as the number of injured neurons in cortical layers II/III and V/VI, striatum and hippocampal regions CA1/CA3. Finally, compared to the non-treated TBI animals, AQP or HIF-1α inhibition significantly (p<0.01) improved neurobehavioral outcomes after TBI. Taken together, the present data supports a causal relation between HIF-AQP mediated cerebral edema, secondary neuronal injury, and tertiary behavioral deficits post-TBI. The data further suggests that upstream modulation of the molecular patho-trajectory effectively ameliorates both neuronal injury and behavioral deficits post-TBI.