Cinnamaldehyde has Antifibrotic Effects on Rats with Epidural Fibrosis.

BACKGROUND: Laminectomy is a widely employed surgical procedure for the treatment of spinal stenosis, but it may lead to epidural fibrosis (EF) and failed back surgery syndrome. Cinnamaldehyde, a phenylpropanoid found in cinnamon, has demonstrated antioxidant and anti-inflammatory properties. In the present study, we hypothesized that topical application and systemic administration of cinnamaldehyde could be helpful in the prevention of EF in a rat laminectomy model. METHODS: The rats were randomly assigned to control, local, and systemic Tween-80 and local and systemic cinnamaldehyde experimental groups (n = 6, per group). In the control group, just laminectomy was performed. In local treatment groups, applications were done just after the laminectomy onto dura. In systemic treatment groups, intraperitoneal administrations were performed following skin suturing. The degree of epidural fibrosis was evaluated macroscopically and histopathologically 4 weeks later. RESULTS: Macroscopic assessment revealed decreased EF with both topical and systemic cinnamaldehyde application, whereas microscopic examination results were not significant. CONCLUSIONS: Our findings provide the first experimental evidence of cinnamaldehyde's potential protective effects against EF.

Neuroprotective Effects of Niacin on Ischemia/Reperfusion Injury of the Rabbit Spinal Cord.

OBJECTIVE: Previous studies have shown niacin has neuroprotective effects on the central nervous system. However, its specific effect on spinal cord ischemia/reperfusion injury has not yet been explored. This study aims to evaluate whether niacin can contribute neuroprotective effects on spinal cord ischemia/reperfusion injury. METHODS: Rabbits were randomized into 4 groups of 8 animals: group I (control), group II (ischemia), group III (30 mg/kg methylprednisolone, intraperitoneal), and group IV (500 mg/kg niacin, intraperitoneal). The rabbits in group IV were premedicated with niacin for 7 days prior to inducing ischemia/reperfusion injury. The control group was subjected only to a laparotomy, while the remaining groups underwent spinal cord ischemia through a 20-minute occlusion of the aorta caudal to the left renal artery. Following the procedure, levels of catalase, malondialdehyde, xanthine oxidase, myeloperoxidase, and caspase-3 were analyzed. Ultrastructural, histopathological, and neurological evaluations were also performed. RESULTS: Spinal cord ischemia/reperfusion injury resulted in increased levels of xanthine oxidase, malondialdehyde, myeloperoxidase, and caspase-3, with a concomitant decrease in catalase levels. Treatment with methylprednisolone and niacin led to decreased levels of xanthine oxidase, malondialdehyde, myeloperoxidase, and caspase-3 and an increase in catalase. Both methylprednisolone and niacin treatments demonstrated improvements in histopathological, ultrastructural, and neurological assessments. CONCLUSIONS: Our findings suggest that niacin has antiapoptotic, anti-inflammatory, antioxidant, and neuroprotective effects at least equal to methylprednisolone in ischemia/reperfusion injury of the spinal cord. This study is the first to report the neuroprotective impact of niacin on spinal cord ischemia/reperfusion injury. Further research is warranted to elucidate the role of niacin in this context.

Cerebrolysin Amelioration of Spinal Cord Ischemia/ Reperfusion Injury in Rabbit Model.

AIM: To investigate the effects of cerebrolysin on inflammation, oxidative stress, apoptosis, and neurologic recovery in the setting of an experimental rabbit model of spinal cord ischemia/reperfusion injury (SCIRI). MATERIAL AND METHODS: Rabbits were randomly divided into five groups: control, ischemia, vehicle, methylprednisolone (30 mg/kg), and cerebrolysin (5 ml/kg) group. The rabbits in the control group underwent only laparotomy; the other groups underwent spinal cord ischemia and reperfusion injury for 20 minutes. Neurologic examination after 24 hours was based on the Modified Tarlov scale. Myeloperoxidase activities, catalase and malondialdehyde levels, and caspase-3 concentrations were determined in serum and tissue samples. Serum xanthine oxidase levels were studied and histopathological and ultrastructural changes were examined. RESULTS: After SCIRI, serum and tissue myeloperoxidase activities, malondialdehyde levels, caspase-3 concentrations, and serum xanthine oxidase activities were increased (p < 0.01?0.001). Catalase levels were significantly diminished (p < 0.001). Cerebrolysin treatment correlated with reduced myeloperoxidase and xanthine oxidase activities, malondialdehyde levels and caspase-3 concentrations; and with increased catalase levels (p < 0.001, for all). The cerebrolysin group showed improved histopathological, ultrastructural, and neurological outcomes. CONCLUSION: For the first time in the literature, the current study reports anti-inflammatory, antioxidant, antiapoptotic, and neuroprotective effects of cerebrolysin in a SCIRI rabbit model.

Anti-Inflammatory, Antioxidant and Neuroprotective Effects of Niacin on Mild Traumatic Brain Injury in Rats.

AIM: To study the effects of niacin, a water-soluble vitamin, on inflammation, oxidative stress and apoptotic processes observed after mild traumatic brain injury (TBI). MATERIAL AND METHODS: A total of 25 Wistar albino male rats were randomly divided into control (n=9), TBI + Placebo group (n=9), TBI + niacin (500 mg/kg; n=7) groups. Mild TBI was performed under anesthesia by dropping a 300 g weight from a height of 1 meter onto the skull. Behavioral tests were applied before and 24 hours after TBI. Luminol and lucigenin levels and tissue cytokine levels were measured. Histopathological damage was scored in brain tissue. RESULTS: After mild TBI, luminol and lucigenin levels were increased (p < 0.001), and their levels were decreased with niacin treatment (p < 0.01-p < 0.001). An increased score was obtained with trauma in the tail suspension test (p < 0.01), showing depressive behavior. The number of entries to arms in Y-maze test were decreased in TBI group compared to pre-traumatic values (p < 0.01), while discrimination (p < 0.05) and recognition indices (p < 0.05) in object recognition test were decreased with trauma, but niacin treatment did not change the outcomes in behavioral tests. Levels of the anti-inflammatory cytokine IL-10 were decreased with trauma, and increased with niacin treatment (p < 0.05). The histological damage score was increased with trauma (p < 0.001), and decreased with niacin treatment in the cortex (p < 0.05), and hippocampal dentate gyrus region (p < 0.01). CONCLUSION: Niacin treatment after mild TBI inhibited trauma-induced production of reactive oxygen derivatives and elevated the anti-inflammatory IL-10 level. Niacin treatment ameliorated the histopathologically evident damage.

Surgical Management Thoracolumbar Fractures in Patients with Ankylosing Spondylitis: Technical Note with Case Series.

OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory joint disease. Complications such as traumatic spinal fractures are mostly caused by hyperextension and are unstable. We report the cases of 5 patients with AS surgically treated for thoracolumbar fractures. METHODS AND RESULTS: We shared our experience of posterior stabilization surgery performed for the treatment of thoracolumbar fractures after traumas such as fall-accident in patients with AS. Patients were all men, and their ages were between 52 and 77 years. The first 3 patients woke up with neurologic deficits and were managed surgically under general anesthesia. We managed the last 2 patients with unilateral short-level stabilization under local anesthesia followed by bilateral long-level stabilization under general anesthesia. No neurologic deterioration was found in the postoperative examination of these 2 patients. We assume that the reason for neurologic deterioration after general anesthesia is the relaxation of muscles. All 3 columns of the spine are affected in patients with AS and the stability is provided by the tone of the muscles around the spine. CONCLUSIONS: To prevent postoperative neurologic complications after the surgical treatment of traumatic hyperextension thoracic and lumbar fractures in patients with AS, we recommend securing the fracture level with unilateral short-level stabilization under local anesthesia and then completing the operation with general anesthesia.

Mildronate Has Ameliorative Effects on the Experimental Ischemia/Reperfusion Injury Model in the Rabbit Spinal Cord.

BACKGROUND: Mildronate is a useful anti-ischemic agent and has antiinflammatory, antioxidant, and neuroprotective activities. The aim of this study is to investigate the potential neuroprotective effects of mildronate in the experimental rabbit spinal cord ischemia/reperfusion injury (SCIRI) model. METHODS: Rabbits were randomized into 5 groups of 8 animals as groups 1 (control), 2 (ischemia), 3 (vehicle), 4 (30 mg/kg methylprednisolone [MP]), and 5 (100 mg/kg mildronate). The control group underwent only laparotomy. The other groups have the spinal cord ischemia model by a 20-minute aortic occlusion just caudal to the renal artery. The malondialdehyde and catalase levels and caspase-3, myeloperoxidase, and xanthine oxidase activities were investigated. Neurologic, histopathologic, and ultrastructural evaluations were also performed. RESULTS: The serum and tissue myeloperoxidase, malondialdehyde, and caspase-3 values of the ischemia and vehicle groups were statistically significantly higher than those of the MP and mildronate groups (P < 0.001). Serum and tissue catalase values of the ischemia and vehicle groups were statistically significantly lower than those of the control, MP, and mildronate groups (P < 0.001). The histopathologic evaluation showed a statistically significantly lower score in the mildronate and MP groups than in the ischemia and vehicle groups (P < 0.001). The modified Tarlov scores of the ischemia and vehicle groups were statistically significantly lower than those of the control, MP, and mildronate groups (P < 0.001). CONCLUSIONS: This study presented the antiinflammatory, antioxidant, antiapoptotic, and neuroprotective effects of mildronate on SCIRI. Future studies will elucidate its possible use in clinical settings in SCIRI.

Antioxidant and neuroprotective effects of dexpanthenol in rats induced with traumatic brain injury.

Trauma-induced primary damage is followed by secondary damage, exacerbating traumatic brain injury (TBI). Dexpanthenol has been shown to protect tissues against oxidative damage in various inflammation models. This study aimed to investigate possible antioxidant and neuroprotective effects of dexpanthenol in TBI. Wistar albino male rats were randomly assigned to control (n = 16), trauma (n = 16) and dexpanthenol (500 mg/kg; n = 14) groups. TBI was induced under anesthesia by dropping a 300 g weight from 70-cm height onto the skulls of the rats. Twenty-four hours after the trauma, the rats were decapitated and myeloperoxidase (MPO) levels, luminol- and lucigenin-enhanced chemiluminescence (CL), malondialdehyde (MDA) levels, superoxide dismutase (SOD) levels, and catalase (CAT) and caspase-3 activities were measured in brain tissues. Following transcardiac paraformaldehyde perfusion, histopathological damage was graded on hematoxylin-eosin-stained brain tissues. In the trauma group, MPO level, caspase-3 activity and luminol-lucigenin CL levels were elevated (p < 0.05-0.001) when compared to controls; meanwhile in the dexpanthenol group these increases were not seen (p < 0.05-0.001) and MDA levels were decreased (p < 0.05). Decreased SOD and CAT activities (p < 0.01) in the vehicle-treated TBI group were increased above control levels in the dexpanthenol group (p < 0.05-0.001). in the dexpanthenol group there was relatively less neuronal damage observed microscopically in the cortices after TBI. Dexpanthenol reduced oxidative damage, suppressed apoptosis by stimulating antioxidant systems and alleviated brain damage caused by TBI. Further experimental and clinical investigations are needed to confirm that dexpanthenol can be administered in the early stages of TBI.

Possible anti-inflammatory, antioxidant, and neuroprotective effects of apigenin in the setting of mild traumatic brain injury: an investigation.

OBJECTIVE: Apigenin is a plant flavone proven with biological properties such as anti-inflammatory, antioxidant, and antimicrobial effects. This study, it was aimed to examine the possible anti-inflammatory, antioxidant, and neuroprotective effects of apigenin in the setting of the mild traumatic brain injury (TBI) model. METHODS: Wistar albino male rats were randomly assigned to groups: control (n = 9), TBI (n = 9), TBI + vehicle (n = 8), and TBI + apigenin (20 and 40 mg/kg, immediately after trauma; n = 6 and n = 7). TBI was performed by dropping a 300 g weight from a height of 1 m onto the skull under anesthesia. Neurological examination and tail suspension tests were applied before and 24 h after trauma, as well as Y-maze and object recognition tests, after that rats were decapitated. In brain tissue, luminol- and lucigenin-enhanced chemiluminescence levels and cytokine ELISA levels were measured. Histological damage was scored. Data were analyzed with one-way ANOVA. RESULTS: After TBI, luminol (p < .001) and lucigenin (p < .001) levels increased, and luminol and lucigenin levels decreased with apigenin treatments (p < .01-.001). The tail suspension test score increased with trauma (p < .01). According to the pre-traumatic values, the number of entrances to the arms (p < .01) in the Y-maze decreased after trauma (p < .01). In the object recognition test, discrimination (p < .05) and recognition indexes (p < .05) decreased with trauma. There was no significant difference among trauma apigenin groups in behavioral tests. Interleukin (IL)-10 levels, one of the anti-inflammatory cytokines, decreased with trauma (p < .05), and increased with 20 and 40 mg apigenin treatment (p < .001 and p < .01, respectively). The histological damage score in the cortex was decreased in the apigenin 20 mg treatment group significantly (p < .05), but the decrease observed in the apigenin 40 mg group was not significant. CONCLUSION: The results of this study revealed that apigenin 20 and 40 mg treatment may have neuroprotective effects in mild TBI via decreasing the level of luminol and lucigenin and increasing the IL-10 levels. Additionally, apigenin 20 mg treatment ameliorated the trauma-induced cortical tissue damage.

Primary Hydatid Cyst of Lumbar Paravertebral Muscle.

Hydatid cyst disease as a zoonosis usually infests the liver and lungs, and it rarely affects muscles. Here, we presented a 36-year-old female patient with low back pain. Radiological evaluation revealed a soft tissue lesion located at the left paravertebral region without vertebral invasion. Surgical exploration and removal of the cyst were performed. The pathological diagnosis was hydatid cyst. After the surgery, the patient was treated with albendazole which is used to decrease the consequences of spillage and the possibility of recurrence. Hydatid cyst disease is rarely seen in paravertebral muscle tissue and needs to be correctly managed. Primary muscle involvement of hydatid cyst must be kept in mind for differential diagnosis of paravertebral cystic mass lesions.

Neuroprotective Effects of Dexpanthenol on Rabbit Spinal Cord Ischemia/Reperfusion Injury Model.

OBJECTIVE: Dexpanthenol (DXP) reportedly protects tissues against oxidative damage in various inflammation models. This study aimed to evaluate its effects on oxidative stress, inflammation, apoptosis, and neurological recovery in an experimental rabbit spinal cord ischemia/reperfusion injury (SCIRI) model. METHODS: Rabbits were randomized into 5 groups of 8 animals each: group 1 (control), group 2 (ischemia), group 3 (vehicle), group 4 (methylprednisolone, 30 mg/kg), and group 5 (DXP, 500 mg/kg). The control group underwent laparotomy only, whereas other groups were subjected to spinal cord ischemia by aortic occlusion (just caudal to the 2 renal arteries) for 20 min. After 24 h, a modified Tarlov scale was employed to record neurological examination results. Malondialdehyde and caspase-3 levels and catalase and myeloperoxidase activities were analyzed in tissue and serum samples. Xanthine oxidase activity was measured in the serum. Histopathological and ultrastructural evaluations were also performed in the spinal cord. RESULTS: After SCIRI, serum and tissue malondialdehyde and caspase-3 levels and myeloperoxidase and serum xanthine oxidase activities were increased (P < 0.05-0.001). However, serum and tissue catalase activity decreased significantly (P < 0.001). DXP treatment was associated with lower malondialdehyde and caspase-3 levels and reduced myeloperoxidase and xanthine oxidase activities but increased catalase activity (P < 0.05-0.001). Furthermore, DXP was associated with better histopathological, ultrastructural, and neurological outcome scores. CONCLUSIONS: This study was the first to evaluate antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective effects of DXP on SCIRI. Further experimental and clinical investigations are warranted to confirm that DXP can be administered to treat SCIRI.

Effect of Preoperative Serum Transthyretin Levels on Postoperative Clinical Results and Morbidity in Patients Undergoing Spinal Surgery.

Introduction This study aims to investigate the effects of preoperative serum transthyretin (TTR) levels on surgical success, pain scores, and postoperative morbidity. Methods Note that, in our clinic, 188 patients who were operated for spinal pathologies between June 2010 and January 2011 were included in this study. Blood samples were drawn from all patients on the morning of surgery and then serum TTR measurements were made. Demographic data of all patients were collected, and then their preoperative and postoperative neurological examinations, Karnofsky scores, visual analog scale (VAS) scores, Oswestry Disability Index (ODI) scores, postoperative infection and wound healing status, hospital stay, and morbidity levels were recorded and TTR levels were compared. Results When preoperative TTR level of patients were low, their Karnofsky scores decreased, ODI scores increased, the early postoperative VAS and late postoperative VAS values increased, and the length of hospital stay was increased. Moreover, in patients with low TTR levels, postoperative Karnofsky scores were lower, postoperative ODI levels were higher, postoperative early and late VAS scores were higher, hospital stays were longer, peroperative complication rates were higher, wound infection rates were higher, the delay in wound site healing was higher, and the morbidity rate was higher. Conclusion Consequently, preoperative low TTR levels have been reported to be an effective parameter that can be used to predict surgical results, wound infection and wound site healing status, perioperative complications, and morbidity in spinal surgery.

Biochemical, pathological and ultrastructural investigation of whether lamotrigine has neuroprotective efficacy against spinal cord ischemia reperfusion injury.

INTRODUCTION: Lamotrigine, an anticonvulsant drug with inhibition properties of multi-ion channels, has been shown to be able to attenuates secondary neuronal damage by influencing different pathways. The aim of this study was to look into whether lamotrigine treatment could protect the spinal cord from experimental spinal cord ischemia-reperfusion injury. MATERIALS AND METHODS: Thirty-two rats, eight rats per group, were randomly assigned to the sham group in which only laparotomy was performed, and to the ischemia, methylprednisolone and lamotrigine groups, where the infrarenal aorta was clamped for thirty minutes to induce spinal cord ischemia-reperfusion injury. Tissue samples belonging to spinal cords were harvested from sacrificed animals twenty-four hours after reperfusion. Tumor necrosis factor-alpha levels, interleukin-1 beta levels, nitric oxide levels, superoxide dismutase activity, catalase activity, glutathione peroxidase activity, malondialdehyde levels and caspase-3 activity were studied. Light and electron microscopic evaluations were also performed to reveal the pathological alterations. Basso, Beattie, and Bresnahan locomotor scale and the inclined-plane test was used to evaluate neurofunctional status at the beginning of the study and just before the animals were sacrificed. RESULTS: Lamotrigine treatment provided significant improvement in the neurofunctional status by preventing the increase in cytokine expression, increased lipid peroxidation and oxidative stress, depletion of antioxidant enzymes activity and increased apoptosis, all of which contributing to spinal cord damage through different paths after ischemia reperfusion injury. Furthermore, lamotrigine treatment has shown improved results concerning the histopathological and ultrastructural scores and the functional tests. CONCLUSION: These results proposed that lamotrigine may be a useful therapeutic agent to prevent the neuronal damage developing after spinal cord ischemia-reperfusion injury.

Neuroprotective Effect of Cinnamaldehyde on Secondary Brain Injury After Traumatic Brain Injury in a Rat Model.

OBJECTIVE: The aim of this study was to investigate the possible neuroprotective effects of cinnamaldehyde (CA) on secondary brain injury after traumatic brain injury (TBI) in a rat model. METHODS: Rats were randomly divided into 4 groups: control (n = 9), TBI (n = 9), vehicle (0.1% Tween 80; n = 8), and CA (100 mg/kg) (n = 9). TBI was induced by the weight-drop model. In brain tissues, myeloperoxidase activity and the levels of luminol-enhanced and lucigenin-enhanced chemiluminescence were measured. Interleukin 1ß, interleukin 6, tumor necrosis factor α, tumor growth factor ß, caspase-3, and cleaved caspase-3 were evaluated with an enzyme-linked immunosorbent assay method. Brain injury was histopathologically graded after hematoxylin-eosin staining. Y-maze and novel object recognition tests were performed before TBI and within 24 hours of TBI. RESULTS: Higher myeloperoxidase activity levels in the TBI group (P < 0.001) were suppressed in the CA group (P < 0.05). Luminol-enhanced and lucigenin-enhanced chemiluminescence, which were increased in the TBI group (P < 0.001, for both), were decreased in the group that received CA treatment (P < 0.001 for both). Compared with the increased histologic damage scores in the cerebral cortex and dentate gyrus of the TBI group (P < 0.001), scores of the CA group were lower (P < 0.001). Decreased number of entries and spontaneous alternation percentage in the Y-maze test of the TBI group (P < 0.05 and P < 0.01, respectively) were not evident in the CA group. CONCLUSIONS: CA has shown neuroprotective effects by limiting neutrophil recruitment, suppressing reactive oxygen species and reducing histologic damage and acute hippocampal dysfunction.

Effects of Ganoderma lucidum Polysaccharides on Different Pathways Involved in the Development of Spinal Cord Ischemia Reperfusion Injury: Biochemical, Histopathologic, and Ultrastructural Analysis in a Rat Model.

OBJECTIVE: Inflammation and oxidative stress are 2 important factors in the emergence of paraplegia associated with spinal cord ischemia-reperfusion injury (SCIRI) after thoracoabdominal aortic surgery. Here it is aimed to investigate the effects of Ganoderma lucidum polysaccharide (GLPS) on SCIRI. METHODS: Rats were randomly selected into 4 groups of 8 animals each: sham, ischemia, methylprednisolone, and GLPS. To research the impacts of various pathways that are efficacious in formation of SCIRI, tumor necrosis factor α, interleukin 1ß, nitric oxide, superoxide dismutase levels, and catalase, glutathione peroxidase activities, malondialdehyde levels, and caspase-3 activity were measured in tissues taken from the spinal cord of rats in all groups killed 24 hours after ischemia reperfusion injury. The Basso, Beattie, and Bresnahan locomotor scale and inclined plane test were used for neurologic assessment before and after SCIRI. In addition, histologic and ultrastructural analyses of tissue samples in all groups were performed. RESULTS: SCIRI also caused marked increase in tissue tumor necrosis factor α, interleukin 1ß, nitric oxide, malondialdehyde levels, and caspase-3 activity, because of inflammation, increased free radical generation, lipid peroxidation, and apoptosis, respectively. On the other hand, SCIRI caused significant reduction in tissue superoxide dismutase, glutathione peroxidase, and catalase activities. Pretreatment with GLPS likewise diminished the level of the spinal cord edema, inflammation, and tissue injury shown by pathologic and ultrastructural examination. Pretreatment with GLPS reversed all these biochemical changes and improved the altered neurologic status. CONCLUSIONS: These outcomes propose that pretreatment with GLPS prevents progression of SCIRI by alleviating inflammation, oxidation, and apoptosis.

Effect of Preoperative Serum Transthyretin Levels on Postoperative Clinical Results and Morbidity in Patients Undergoing Spinal Surgery.

INTRODUCTION: This study aims to investigate the effects of preoperative serum transthyretin (TTR) levels on surgical success, pain scores, and postoperative morbidity. METHODS: Note that, in our clinic, 188 patients who were operated for spinal pathologies between June 2010 and January 2011 were included in this study. Blood samples were drawn from all patients on the morning of surgery, and then, serum TTR measurements were made. Demographic data of all patients were collected, and then their preoperative and postoperative neurological examinations, Karnofsky scores, Visual Analog Scale (VAS) scores, Oswestry disability index (ODI) scores, postoperative infection and wound healing status, hospital stay, and morbidity levels were recorded, and TTR levels were compared. RESULTS: When preoperative TTR level of patients was low, their Karnofsky scores decreased, ODI scores increased, the early postoperative VAS and late postoperative VAS values increased, and the length of hospital stay was increased. Moreover, in patients with low TTR levels, postoperative Karnofsky scores were lower, postoperative ODI levels were higher, postoperative early and late VAS scores were higher, hospital stays were longer, peroperative complication rates were higher, wound infection rates were higher, the delay in wound site healing was higher, and the morbidity rate was higher. CONCLUSION: Consequently, preoperative low TTR levels have been reported to be an effective parameter that can be used to predict surgical results, wound infection and wound site healing status, perioperative complications, and morbidity in spinal surgery.

Amelioration of Cerebral Vasospasm and Secondary Injury by Vigabatrin After Experimental Subarachnoid Hemorrhage in the Rabbit.

BACKGROUND: Vigabatrin, an antiepileptic drug, increases the level of gamma aminobutyric acid in the brain by inhibiting its catabolism. Because gamma aminobutyric acid has been proved to have vasodilatory effects, in the present study, we investigated the effect of vigabatrin to treat experimental subarachnoid hemorrhage (SAH)-induced vasospasm. METHODS: A total of 30 New Zealand white rabbits were divided into 3 groups of 10 each: the control group, SAH group, and vigabatrin group. Experimental SAH was established by injection of autologous arterial blood into the cisterna magna. In the vigabatrin group, the rabbits were administered vigabatrin for 3 days after induction of the SAH. The first dose of vigabatrin was given 2 hours after SAH induction. A daily dose of 500 mg/kg vigabatrin was administered intraperitoneally. After 3 days, the rabbits were sacrificed, and the brains were removed, together with the cerebellum and brainstem. The basilar artery wall thickness and lumen areas were measured. The neuronal degeneration in the hippocampus (CA1, CA3, and dentate gyrus) was also evaluated. RESULTS: The arterial wall thickness of the vigabatrin group was less than that in the SAH group (P < 0.001), and the mean luminal area of the vigabatrin group was greater than that in the SAH group (P < 0.001). Additionally, the hippocampal neuronal degeneration score of the vigabatrin group was lower than that of the SAH group (P < 0.001). CONCLUSION: These findings have indicated that vigabatrin has a vasodilatory effect in an experimental SAH model in the rabbit. Moreover, it showed a neuroprotective effect in the hippocampal neurons against secondary injury induced by SAH.

Blocking VEGF by Bevacizumab Attenuates VEGF-Induced Vasospasm After Experimental Subarachnoid Hemorrhage in Rabbits.

OBJECTIVE: Vasospasm after subarachnoid hemorrhage (SAH) plays a vital role in the development of delayed cerebral ischemia. Anti- vascular endothelial growth factor (VEGF) antibodies, like bevacizumab (BEV), may attenuate VEGF-stimulated angiogenesis, reduced vascular cell proliferation, and improve vasospasm after SAH. METHODS: Thirty-two adult male New Zealand white rabbits were randomly divided into 4 groups of 8 rabbits in each group: group 1 (control); group 2 (SAH); group 3 (SAH + vehicle); and group 4 (SAH + BEV). BEV (5 mg/kg, intraperitoneally) was administered 5 minutes after the intracisternal blood injection and continued for 72 hours once per day in the same dose for group 4. Animals were sacrificed 72 hours after SAH. Basilar artery cross-sectional areas, arterial wall thicknesses, and hippocampal degeneration scores were evaluated in all groups. RESULTS: VEGF is associated with the narrowing of the basilar artery. Treatment with BEV statistically significantly increased the cross-sectional area of the basilar artery when compared with the SAH and the vehicle groups. Basilar artery wall thicknesses in the BEV group was statistically significant smaller than in the SAH and vehicle groups. The hippocampal degeneration scores for the BEV and control groups were similar and significantly lower than those for the SAH and vehicle groups. CONCLUSIONS: Cellular proliferation and subsequent vessel wall thickening is a reason to delay cerebral ischemia and deterioration of the neurocognitive function. Intraperitoneal administration of BEV was found to attenuate cerebral vasospasm and prevent delayed cerebral ischemia and improve neurocognitive function after SAH in rabbits.

The Vasorelaxant and Neuroprotective Effects of Mildronate in A Rabbit Subarachnoid Hemorrhage Model.

AIM: To investigate the effects of an anti-ischemic agent, mildronate, on subarachnoid hemorrhage-induced vasospasm. MATERIAL AND METHODS: Rabbits were randomly divided into four groups: control, subarachnoid hemorrhage (SAH), vehicle, and mildronate (n=8 animals per group). In the treatment group, 200 mg/kg of mildronate were intraperitoneally administered 5 minutes after the procedure and continued for 3 days as daily administrations of the same dose. At the end of the third day, the cerebrum, cerebellum, and brain stem were perfused, fixated, and removed for histopathological examination. Tissues were examined for arterial wall thickness, luminal area, and hippocampal neuronal degeneration. RESULTS: Mildronate group showed significantly increased luminal area and reduced wall thickness of the basilar artery compared with the subarachnoid hemorrhage group. In addition, the hippocampal cell degeneration score was significantly lower in the mildronate group than in the SAH and vehicle groups. CONCLUSION: These results show that mildronate exerts protective effects against SAH-induced vasospasm and secondary neural injury.

High-resolution diffusion tensor magnetic resonance imaging of the brainstem safe entry zones.

Operative management of intrinsic brainstem lesions remains challenging despite advances in electrophysiological monitoring, neuroimaging, and neuroanatomical knowledge. Surgical intervention in this region requires detailed knowledge of adjacent critical white matter tracts, brainstem nuclei, brainstem vessels, and risks associated with each surgical approach. Our aim was to systematically verify internal anatomy associated with each brainstem safety entry zone (BSEZ) via neuroimaging modalities commonly used in pre-operative planning, namely high-resolution magnetic resonance imaging (MRI) and diffusion tensor tractography (DTT). Twelve BSEZs were simulated in eight, formalin-fixed, cadaveric brains. Specimens then underwent radiological investigation including T2-weighted imaging and DTT using 4.7 T MRI to verify internal anatomic relationships between simulated BSEZs and adjacent critical white matter tracts and nuclei. The distance between simulated BSEZs and pre-defined, adjacent critical structures was systemically recorded. Entry points and anatomic limits on the surface of the brainstem are described for each BSEZ, along with description of potential neurological sequelae if such limits are violated. With high-resolution imaging, we verified a maximal depth for each BSEZ. The relationship between proposed safe entry corridors and adjacent critical structures within the brainstem is quantified. In combination with tissue dissection, high-resolution MR diffusion tensor imaging allows the surgeon to develop a better understanding of the internal architecture of the brainstem, particularly as related to BSEZs, prior to surgical intervention. Through a careful study of such imaging and use of optimal surgical corridors, a more accurate and safe surgery of brainstem lesions may be achieved.