Extraforaminal Microdiscectomy for Upper Lumbar Disc Herniations: A Minimally Invasive Alternative Surgical Approach.

BACKGROUND: Various methods and techniques have been developed for extraforaminal decompression, particularly for far lateral lumbar disc herniation. Distinct anatomical differences are noticeable in the upper levels of the lumbar spine, which may complicate the related surgical approach. This study aimed to determine the safety and efficiency of the far lateral extraforaminal approach for the upper lumbar disc. METHODS: L1-2 and L2-3 migrated lumbar disc herniations were defined as upper lumbar disc herniations. 31 consecutive patients with upper lumbar disk herniation who underwent extraforaminal lumbar microdiscectomy between January 2018 and March 2022 were retrospectively investigated. The patients were assessed using the interval history, follow-up lower back and leg pain visual analog scale scores (0-100 mm), the Oswestry Disability Index (%), and modified MacNab criteria. RESULTS: 31 consecutive patients with upper lumbar disk herniation (20 men and 11 women) with a mean age of 52.8 ± 10.8 years (range 31-70 years) underwent extraforaminal lumbar microdiscectomy. The preoperative and postoperative visual analog scale scores and Oswestry Disability Index were significantly different (P < 0.001). According to the modified MacNab criteria, 23 patients showed excellent improvement, 5 showed good improvement, and 3 showed fair improvement; thus, the rate of satisfactory improvement was 90.3% at the 2-year follow-up. No patients required reoperation at the operative level during follow-up. CONCLUSIONS: Extraforaminal lumbar microdiscectomy is a safe and effective minimally invasive surgical technique for treating upper lumbar disc herniation.

An unusual case of pediatric cervical myelopathy due to congenital spinal canal stenosis.

Cervical myelopathy is a condition that is rarely reported in pediatric patients who have movement or neuromuscular disorders. We, herein, present a rare case of cervical myelopathy observed in a 14-year-old patient, who was previously a healthy boy treated with cervical laminoplasty, which was caused by cervical spinal canal stenosis based on multiple level disc herniation. The patient presented to the clinic with spastic and ataxic gait with previous diagnostic challenges. Magnetic resonance imaging showed cervical degenerative changes mainly marked at the C3-C4 and C4-C5 levels, along with canal narrowing and a central high signal cord abnormality on T2-weighted images. A C3-C4 open-door laminoplasty surgery technique was performed. The neurological symptoms and signs improved dramatically following surgery. Subsequently, cervical computed tomography and magnetic resonance imaging showed good decompression of the cervical spinal cord during the 5 years of follow-up with the preservation of the range of movement. We concluded that though it is pretty rare, cervical myelopathy should be considered in diagnosing adolescent patients with gait and balance disorders.

Salvage posterior atlantoaxial fixation techniques: A retrospective study.

OBJECT: Since the atlantoaxial region have critical neurovascular anatomy and limited bone surface for fusion, the application and choice of salvage fixation techniques are highly important. To discuss alternative posterior atlantoaxial fixation surgery techniques. METHODS: We retrospectively surgical records of 22 patients that posterior atlantoaxial fixation techniques were applied. RESULTS: The patients included 11 males and 11 females (mean age: 65.7 years). The fracture type that caused instability is type 2 odontoid fractures (22). In six of these patients alternative stabilization techniques were applied due to anatomical variations, huge venous bleeding and iatrogenic trauma of the screw entry points during surgery. CONCLUSIONS: Owing to anatomical variations, intraoperative challenges, and/or instrumentation failures, performing alternative surgical fixation technique is an important factor that affects the success of stabilization of the atlantoaxial region. Knowledge of salvage techniques especially during the learning curve is vitally important. Surgeons should adapt to intraoperative surgical challenges as required.

Morphometric measurements of safety zones and orientation angles for freehand placement of revision screws in atlas lateral mass.

AIM: To demonstrate the possibility of revision screw placement to the atlas, as well as define the safety zones and orientation angles. MATERIAL AND METHODS: This retrospective study analysed the records of four patients who were operated for AAI earlier. Because they needed revision of Atlas screws, they were re-operated after obtaining the measurements mentioned in this study. In addition, measurements of 50 healthy subjects were included in the study as the control group. Maximum screw lengths were also measured. RESULTS: Safe zone in the ideal sagittal direction were wider. As the screw projection becomes more cephalic direction in the sagittal plane, the safe zone for the screw becomes narrower. With the sagittal angle moving forwards cranially, the screw length becomes longer. CONCLUSION: Atlas lateral mass screws could be safely revised whenever needed. The fact that needs to be considered is that the angular range becomes narrower, and the screw length becomes longer when the screw is directed more cranially.

Posterior realignment of basilar invagination with facet joint distraction technique.

PURPOSE: We describe our experience with management of basilar invagination (BI) with the atlantoaxial dislocation (C1/C2) joint reduction technique, including posterior atlantoaxial internal fixation. MATERIALS AND METHODS: From 2008 to 2018, eleven patients with atlantoaxial dislocation (AAD) and BI underwent surgical reduction using C1/C2 the joint reduction technique with a fibular graft/peek cage placement followed by C1 lateral mass/C2 pedicle screw fixation. In two cases that we originally planned to perform C1/C2 joint reduction, occiput-C2 pedicle screw fixation was performed instead due to intraoperative challenges. Post-operative course and surgical complications will be discussed. RESULTS: A total of 13 patients, with an average age of 30.46 ± 13.23 years (range 12-57), were operated. In one patient, iatrogenic vertebral artery injury occurred without any neurological complication. JOA score improved from 10.45 ± 1.128 to 15.0 ± 1.949 (p < 0.0001, paired t-test). All radiological indices were improved (p at least < 0.001). No construct failure was seen in any of the patients with C1-2 facet joint distraction technique during follow-up, and no additional anterior decompression surgery was required. CONCLUSIONS: C1/C2 joint reduction technique with fibular graft/cervical PEEK cage of BI patients together with AAD seems to be an effective and safe surgical method of treatment.

What is the restorative effect of VEGF inhibitor bevacuzimab against subarachnoid hemorrhage in an experimental model?

BACKGROUND: This study investigated the effect of vascular endothelial growth factor (VEGF) inhibitor bevacuzimab (BVZ) on the rabbit basilar artery using an experimental subarachnoid hemorrhage (SAH) model. METHODS: Eighteen adult male New-Zealand white rabbits were randomly divided into three groups: a control group (n = 6), SAH group (n = 6), and SAH+BVZ group (n = 6). Experimental SAH was created by injecting autologous arterial blood into the cisterna magna. In the treatment group, the subjects were administered a daily dose of 10 mg/kg, intravenous BVZ for 2 days after the SAH. Basilar artery diameters were measured with magnetic resonance angiography (MRA) 72 h after the SAH in all groups. After 72 h, whole brains, including the upper cervical region, were obtained from all the animals after perfusion and fixation of the animal. The wall thickness, luminal area, and the apoptosis at the basilar arteries were evaluated in all groups. RESULTS: BVZ significantly prevented SAH-induced vasospasm confirmed in vivo with MRA imaging with additional suppression of apoptosis on basilar artery wall. DISCUSSION: VEGF inhibition with BVZ has shown to have a vasospasm and apoptosis attenuating effect on basilar artery in a SAH model.

Azathioprine as a Neuroprotective Agent in Experimental Traumatic Spinal Cord Injury.

AIM: To evaluate the protective effects of azathioprine, a macrophage-inhibiting agent, on secondary injury in spinal cord trauma. MATERIAL AND METHODS: A total of 40 Wistar rats were randomly divided into 4 groups. All the animals had undergone T8-10 laminectomy. Except in group I (control), all the animals were exposed to spinal cord trauma at the T9 level. Animals in group II (trauma) received no treatment following trauma. Animals in group 3 (treatment) and group IV (vehicle) were given intraperitoneal azathioprine 4 mg/kg and saline 2 ml, respectively, 30 minutes after the trauma. Half of the animals in each group were sacrificed 24 hours after injury and specimens were used for biochemical and immunohistochemical evaluations. The rest of the animals were followed-up for 4 weeks in terms of neurological functions and were also sacrificed to perform the histopathological analysis. RESULTS: Significant decrease in apoptotic cells and improved neurological function were observed in the animals treated with azathioprine. Biological and immunohistochemical analysis also showed less oxidative stress in this group compared to those without treatment. CONCLUSION: Azathioprine, a potent macrophage-inhibiting agent, has been shown to decrease the extent of secondary injury following spinal cord trauma.

Contributions of 12/15-Lipoxygenase to Bleeding in the Brain Following Ischemic Stroke.

Ischemic strokes are caused by one or more blood clots that typically obstruct one of the major arteries in the brain, but frequently also result in leakage of the blood-brain barrier and subsequent hemorrhage. While it has long been known that the enzyme 12/15-lipoxygenase (12/15-LOX) is up-regulated following ischemic strokes and contributes to neuronal cell death, recent research has shown an additional major role for 12/15-LOX in causing this hemorrhagic transformation. These findings have important implications for the use of 12/15-LOX inhibitors in the treatment of stroke.

Increased 12/15-Lipoxygenase Leads to Widespread Brain Injury Following Global Cerebral Ischemia.

Global ischemia following cardiac arrest is characterized by high mortality and significant neurological deficits in long-term survivors. Its mechanisms of neuronal cell death have only partially been elucidated. 12/15-lipoxygenase (12/15-LOX) is a major contributor to delayed neuronal cell death and vascular injury in experimental stroke, but a possible role in brain injury following global ischemia has to date not been investigated. Using a mouse bilateral occlusion model of transient global ischemia which produced surprisingly widespread injury to cortex, striatum, and hippocampus, we show here that 12/15-LOX is increased in a time-dependent manner in the vasculature and neurons of both cortex and hippocampus. Furthermore, 12/15-LOX co-localized with apoptosis-inducing factor (AIF), a mediator of non-caspase-related apoptosis in the cortex. In contrast, caspase-3 activation was more prevalent in the hippocampus. 12/15-lipoxygenase knockout mice were protected against global cerebral ischemia compared to wild-type mice, accompanied by reduced neurologic impairment. The lipoxygenase inhibitor LOXBlock-1 similarly reduced neuronal cell death both when pre-administered and when given at a therapeutically relevant time point 1 h after onset of ischemia. These findings suggest a pivotal role for 12/15-LOX in both caspase-dependent and caspase-independent apoptotic pathways following global cerebral ischemia and suggest a novel therapeutic approach to reduce brain injury following cardiac arrest.

Neuroprotective Effects of Pregabalin Against Spinal Cord Ischemia-Reperfusion Injury in Rats.

AIM: To evaluate the effect of pregabalin pre-treatment on spinal cord ischemia-reperfusion (I/R) injury and compare with methylprednisolone (MP). MATERIAL AND METHODS: Thirty-two rats were randomly divided into four groups as follow: Group 1 (sham)(n=8), group 2 (ischemia only)(n=8), group 3 (30 mg/kg pregabalin)(n=8), and group 4 (30 mg/kg methylprednisolone)(n=8). Laparotomy was performed without aortic clamp in the sham group. All animals were sacrificed 24 hours after surgery. The spinal cord tissue samples were harvested and caspase-3 activity, tumor necrosis factor-alpha (TNF-α) and Interleukin-1 Beta (IL-1ß) levels, catalase (CAT) activity, glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) levels malondialdehyde (MDA) levels and nitric oxide (NO) levels were analyzed to investigate the effects of different excitatory and inflammatory pathways in mechanism of I/R injury. Ultrastructural and histopathological examinations were carried out. Neurological recovery was measured by Basso, Beattie, Bresnahan (BBB) test and Inclined Plane Test. RESULTS: Decresead caspase-3 activity and decreased inflammatory markers like TNF-α, IL-1ß, and decresaed excitotatory pathways like CAT, GPx, MDA, NO and SOD were observed in both pregabalin pre-treatment and MP treatment groups. Pregabalin pre-treatment produced better ultrastructural results compared to MP treatment, as with histopathological examination. Pregabalin group showed better recovery compared to MP treament group according to BBB scoring system. CONCLUSION: Pregabalin pre-treatmet and MP treatment both has neuroprotective effect on I/R injury by decreasing caspase dependant apoptosis, and inflammatory and oxidative stress markers. In addition, pregabalin pre-treatment had better clinical effects compared to MP treatment.

Treatment with FTY720 has no beneficial effects on short-term outcome in an experimental model of intracerebral hemorrhage.

BACKGROUND: No evidence-based therapy is available for patients with acute intracerebral hemorrhage (ICH). In view of the profound inflammatory reaction in the perilesional tissue, we investigated in a well-characterized experimental model whether the administration of the immunomodulator fingolimod (FTY720) is neuroprotective in acute ICH. METHODS: ICH was induced by means of a stereotactic intrastriatal injection of collagenase type VII-S. FTY720 (1 mg/kg) was administered intraperitoneally 1 h after ICH induction. Hematoma volume was assessed spectrophotometrically at 24 h after ICH induction. The following endpoints were determined at 24 and 72 h, respectively: mortality rate and neurologic outcomes, edema formation, and MMP-9 activity. RESULTS: Twenty-four hour after ICH induction, hematoma volume was not statistically different between groups. No difference was found in mortality and neurologic outcomes at 24 and 72 h between FTY720 treated mice and controls. Edema formation was present in both groups on the ipsilateral side with no statistical difference between groups at both time points. No difference was found in MMP-9 levels after 24 and 72 h between groups. CONCLUSIONS: Our results suggest that FTY720 has no beneficial effects in the acute phase of experimental ICH.

Gene-Silencing Screen for Mammalian Axon Regeneration Identifies Inpp5f (Sac2) as an Endogenous Suppressor of Repair after Spinal Cord Injury.

Axonal growth and neuronal rewiring facilitate functional recovery after spinal cord injury. Known interventions that promote neural repair remain limited in their functional efficacy. To understand genetic determinants of mammalian CNS axon regeneration, we completed an unbiased RNAi gene-silencing screen across most phosphatases in the genome. We identified one known and 17 previously unknown phosphatase suppressors of injury-induced CNS axon growth. Silencing Inpp5f (Sac2) leads to robust enhancement of axon regeneration and growth cone reformation. Results from cultured Inpp5f(-/-) neurons confirm lentiviral shRNA results from the screen. Consistent with the nonoverlapping substrate specificity between Inpp5f and PTEN, rapamycin does not block enhanced regeneration in Inpp5f(-/-) neurons, implicating mechanisms independent of the PI3K/AKT/mTOR pathway. Inpp5f(-/-) mice develop normally, but show enhanced anatomical and functional recovery after mid-thoracic dorsal hemisection injury. More serotonergic axons sprout and/or regenerate caudal to the lesion level, and greater numbers of corticospinal tract axons sprout rostral to the lesion. Functionally, Inpp5f-null mice exhibit enhanced recovery of motor functions in both open-field and rotarod tests. This study demonstrates the potential of an unbiased high-throughput functional screen to identify endogenous suppressors of CNS axon growth after injury, and reveals Inpp5f (Sac2) as a novel suppressor of CNS axon repair after spinal cord injury. Significance statement: The extent of axon regeneration is a critical determinant of neurological recovery from injury, and is extremely limited in the adult mammalian CNS. We describe an unbiased gene-silencing screen that uncovered novel molecules suppressing axonal regeneration. Inpp5f (Sac2) gene deletion promoted recovery from spinal cord injury with no side effects. The mechanism of action is distinct from another lipid phosphatase implicated in regeneration, PTEN. This opens new pathways for investigation in spinal cord injury research. Furthermore the screening methodology can be applied on a genome wide scale to discovery the entire set of mammalian genes contributing to axonal regeneration.

Warfarin pretreatment reduces cell death and MMP-9 activity in experimental intracerebral hemorrhage.

Little is known about the pathophysiology of oral anticoagulation-associated intracerebral hemorrhage (OAC-ICH). We compared hematoma volume, number of terminal deoxynucleotidyl dUTP nick-end labeling (TUNEL)-positive cells (indicating cell death), MMP-9 levels, and perilesional edema formation between warfarin-treated mice and controls. Intracerebral hemorrhage was induced by an injection of collagenase into the right striatum. Twenty-four hours later, hematoma volume was measured using a photometric hemoglobin assay. Cell death was quantified using TUNEL staining. MMP-9 levels were determined by zymography, and edema formation was assessed via the wet-dry method. Warfarin increased hematoma volume by 2.6-fold. The absolute number of TUNEL-positive cells in the perihematomal zone was lower in warfarin-treated animals (300.5 ± 39.8 cells/mm2) than in controls (430.5 ± 38.9 cells/mm2; p = 0.034), despite the larger bleeding volume. MMP-9 levels were reduced in anticoagulated mice as compared to controls (p = 0.018). Perilesional edema formation was absent in warfarin mice and modestly present in controls. Our results suggest differences in the pathophysiology of OAC-ICH compared to intracerebral hemorrhage occurring under normal coagulation. A likely explanation is that thrombin, a strong inductor of apoptotic cell death and blood-brain barrier disruption, is produced to a lesser extent in OAC-ICH. In humans, however, we assume that the detrimental effects of a larger hematoma volume in OAC-ICH by far outweigh potential protective effects of thrombin deficiency.

Human NgR-Fc decoy protein via lumbar intrathecal bolus administration enhances recovery from rat spinal cord contusion.

Axonal growth and neurological recovery after traumatic spinal cord injury (SCI) is limited by the presence of inhibitory proteins in myelin, several of which act via the NgR1 protein in neurons. A truncated soluble ligand-binding fragment of NgR1 serves as a decoy and promotes recovery in acute and chronic rodent SCI models. To develop the translational potential of these observations, we created a human sequence-derived NgR1(310)-Fc protein. This protein is active in vitro. When the human NgR1 decoy is administered by continuous intracerebroventricular infusion to rats with a spinal contusion injury at doses of 0.09-0.53 mg/kg/d, neurological recovery is improved. Effective doses double the percentage of rats able to bear weight on their hindlimbs. Next, we considered the half-life and distribution of NgR1(310)-Fc after bolus delivery to the lumbar intrathecal space. The protein is found throughout the neuraxis and has a tissue half-life of approximately 2 days in the rat, and 5 days in the nonhuman primate. At an intermittent, once every 4 day, lumbar bolus dosing schedule of 0.14 mg/kg/d, NgR1(310)-Fc promoted locomotor rat recovery from spinal cord contusion at least as effectively as continuous infusion in open field and grid walking tasks. Moreover, the intermittent lumbar NgR1(310)-Fc treatment increased the growth of raphespinal axons into the lumbar spinal cord after injury. Thus, human NgR1(310)-Fc provides effective treatment for recovery from traumatic SCI in this preclinical model with a simplified administration regimen that facilitates clinical testing.

Genetic ablation and short-duration inhibition of lipoxygenase results in increased macroautophagy.

12/15-lipoxygenase (12/15-LOX) is involved in organelle homeostasis by degrading mitochondria in maturing red blood cells and by eliminating excess peroxisomes in liver. Furthermore, 12/15-LOX contributes to diseases by exacerbating oxidative stress-related injury, notably in stroke. Nonetheless, it is unclear what the consequences are of abolishing 12/15-LOX activity. Mice in which the alox15 gene has been ablated do not show an obvious phenotype, and LOX enzyme inhibition is not overtly detrimental. We show here that liver histology is also unremarkable. However, electron microscopy demonstrated that 12/15-LOX knockout surprisingly leads to increased macroautophagy in the liver. Not only macroautophagy but also mitophagy and pexophagy were increased in hepatocytes, which otherwise showed unaltered fine structure and organelle morphology. These findings were substantiated by immunofluorescence showing significantly increased number of LC3 puncta and by Western blotting demonstrating a significant increase for LC3-II protein in both liver and brain homogenates of 12/15-LOX knockout mice. Inhibition of 12/15-LOX activity by treatment with four structurally different inhibitors had similar effects in cultured HepG2 hepatoma cells and SH-SY5Y neuroblastoma cells with significantly increased autophagy discernable already after 2 hours. Hence, our study reveals a link between ablation or inhibition of 12/15-LOX and stimulation of macroautophagy. The enhanced macroautophagy may be related to the known tissue-protective effects of LOX ablation or inhibition under various diseased conditions caused by oxidative stress and ischemia. This could provide an important cleaning mechanism of cells and tissues to prevent accumulation of damaged mitochondria and other cellular components.

Multimodal exercises simultaneously stimulating cortical and brainstem pathways after unilateral corticospinal lesion.

In the context of injury to the corticospinal tract (CST), brainstem-origin circuits may provide an alternative system of descending motor influence. However, subcortical circuits are largely under subconscious control. To improve volitional control over spared fibers after CST injury, we hypothesized that a combination of physical exercises simultaneously stimulating cortical and brainstem pathways above the injury would strengthen corticobulbar connections through Hebbian-like mechanisms. We sought to test this hypothesis in mice with unilateral CST lesions. Ten days after pyramidotomy, mice were randomized to four training groups: (1) postural exercises designed to stimulate brainstem pathways (BS); (2) distal limb-grip exercises preferentially stimulating CST pathways (CST); (3) simultaneous multimodal exercises (BS+CST); or (4) no training (NT). Behavioral and anatomical outcomes were assessed after 20 training sessions over 4 weeks. Mice in the BS+CST training group showed a trend toward greater improvements in skilled limb performance than mice in the other groups. There were no consistent differences between training groups in gait kinematics. Anatomically, multimodal BS+CST training neither increased corticobulbar fiber density of the lesioned CST rostral to the lesion nor collateral sprouting of the unlesioned CST caudal to the lesion. Further studies should incorporate electrophysiological assessment to gauge changes in synaptic strength of direct and indirect pathways between the cortex and spinal cord in response to multimodal exercises.

Study the effects of zonisamide on fine structure of rabbit basilar artery and hippocampus in rabbit subarachnoid hemorrhage model.

BACKGROUND: In this study, we investigated the effect of a novel antiepileptic drug, zonisamide (ZNS), on the basilar artery and hippocampus in a rabbit subarachnoid hemorrhage (SAH) model. METHODS: Three groups of New Zealand white rabbits were used: a sham (non-SAH) group, an SAH + saline group, and SAH + drug treatment group that received ZNS. In the treatment group, the subjects were given ZNS for 3 days after the SAH. Hippocampal sections were evaluated for neural tissue degeneration. Basilar artery lumen areas and arterial wall thickness were also measured in all groups. RESULTS: The mean luminal area of the SAH + ZNS was significantly greater than the SAH + saline group. In addition, the arterial wall thickness of SAH + ZNS group was significantly thinner than the SAH + saline group. The neuronal degeneration scores of the hippocampal CA1 regions in the SAH + ZNS group were significantly lower than the SAH + saline treatment animals. CONCLUSIONS: These results indicate that ZNS has a vasodilatatory effect on the basilar artery and a neuronal protective effect in the CA1 region of the hippocampus in a rabbit SAH model.

Intravenous tPA therapy does not worsen acute intracerebral hemorrhage in mice.

Tissue plasminogen activator (tPA) is the only FDA-approved treatment for reperfusing ischemic strokes. But widespread use of tPA is still limited by fears of inadvertently administering tPA in patients with intracerebral hemorrhage (ICH). Surprisingly, however, the assumption that tPA will worsen ICH has never been biologically tested. Here, we assessed the effects of tPA in two models of ICH. In a mouse model of collagenase-induced ICH, hemorrhage volumes and neurological deficits after 24 hrs were similar in saline controls and tPA-treated mice, whereas heparin-treated mice had 3-fold larger hematomas. In a model of laser-induced vessel rupture, tPA also did not worsen hemorrhage volumes, while heparin did. tPA is known to worsen neurovascular injury by amplifying matrix metalloproteinases during cerebral ischemia. In contrast, tPA did not upregulate matrix metalloproteinases in our mouse ICH models. In summary, our experimental data do not support the assumption that intravenous tPA has a deleterious effect in acute ICH. However, due to potential species differences and the inability of models to fully capture the dynamics of human ICH, caution is warranted when considering the implications of these findings for human therapy.

Following experimental stroke, the recovering brain is vulnerable to lipoxygenase-dependent semaphorin signaling.

Recovery from stroke is limited, in part, by an inhibitory environment in the postischemic brain, but factors preventing successful remodeling are not well known. Using cultured cortical neurons from mice, brain endothelial cells, and a mouse model of ischemic stroke, we show that signaling from the axon guidance molecule Sema3A via eicosanoid second messengers can contribute to this inhibitory environment. Either 90 nM recombinant Sema3A, or the 12/15-lipoxygenase (12/15-LOX) metabolites 12-HETE and 12-HPETE at 300 nM, block axon extension in neurons compared to solvent controls, and decrease tube formation in endothelial cells. The Sema3A effect is reversed by inhibiting 12/15-LOX, and neurons derived from 12/15-LOX-knockout mice are insensitive to Sema3A. Following middle cerebral artery occlusion to induce stroke in mice, immunohistochemistry shows both Sema3A and 12/15-LOX are increased in the cortex up to 2 wk. To determine whether a Sema3A-dependent damage pathway is activated following ischemia, we injected recombinant Sema3A into the striatum. Sema3A alone did not cause injury in normal brains. But when injected into postischemic brains, Sema3A increased cortical damage by 79%, and again, this effect was reversed by 12/15-LOX inhibition. Our findings suggest that blocking the semaphorin pathway should be investigated as a therapeutic strategy to improve stroke recovery.