Glutamate, the major excitatory neurotransmitter in the CNS, is implicated in both normal neurotransmission and excitotoxicity. Numerous in vitro findings indicate that the ionotropic glutamate receptor, AMPAR, can rapidly traffic from intracellular stores to the plasma membrane, altering neuronal excitability. These receptor trafficking events are thought to be involved in CNS plasticity as well as learning and memory. AMPAR trafficking has recently been shown to be regulated by glial release of the proinflammatory cytokine tumor necrosis factor ␣ (TNF␣) in vitro. This has potential relevance to several CNS disorders, because many pathological states have a neuroinflammatory component involving TNF␣. However, TNF␣-induced trafficking of AMPARs has only been explored in primary or slice cultures and has not been demonstrated in preclinical models of CNS damage. Here, we use confocal and image analysis techniques to demonstrate that spinal cord injury (SCI) induces trafficking of AMPARs to the neuronal membrane. We then show that this effect is mimicked by nanoinjections of TNF␣, which produces specific trafficking of GluR2-lacking receptors which enhance excitotoxicity. To determine if TNF␣-induced trafficking affects neuronal cell death, we sequestered TNF␣ after SCI using a soluble TNF␣ receptor, and significantly reduced both AMPAR trafficking and neuronal excitotoxicity in the injury penumbra. The data provide the first evidence linking rapid TNF␣-induced AMPAR trafficking to early excitotoxic secondary injury after CNS trauma in vivo, and demonstrate a novel way in which pathological states hijack mechanisms involved in normal synaptic plasticity to produce cell death.

Sublethal periods of hypoxia or ischemia can induce adaptive mechanisms to protect against subsequent lethal ischemic insults in a process known as ischemic preconditioning. In the present study, we developed a murine model of cerebral preconditioning using several common strains of adult mice. Animals were exposed to sublethal hypoxia (11% oxygen for 2 h) 48 h prior to a 90 min period of transient focal middle cerebral artery occlusion, induced by an intraluminal filament; injury was assessed 24 h later by TTC staining. Infarct volume in hypoxia-preconditioned animals was reduced 46%, 58%, and 64% in C57Bl/6, 129SvEv, and Swiss-Webster ND4 mice relative to their respective untreated controls. This non-invasive murine model of ischemic tolerance should be useful for elucidating the molecular basis of this protection using transgenic and knockout mice.

Subarachnoid hemorrhage (SAH) can lead to devastating neurological outcomes, and there are few pharmacologic treatments available for treating this condition. Both animal and human studies provide evidence of inflammation being a driving force behind the pathology of SAH, leading to both direct brain injury and vasospasm, which in turn leads to ischemic brain injury. Several inflammatory mediators that are elevated after SAH have been studied in detail. While there is promising data indicating that blocking these factors might benefit patients after SAH, there has been little success in clinical trials. One of the key factors that complicates clinical trials of SAH is the variability of the initial injury and subsequent inflammatory response. It is likely that both genetic and environmental factors contribute to the variability of patients' post-SAH inflammatory response and that this confounds trials of anti-inflammatory therapies. Additionally, systemic inflammation from other conditions that affect patients with SAH could contribute to brain injury and vasospasm after SAH. Continuing work on biomarkers of inflammation after SAH may lead to development of patient-specific anti-inflammatory therapies to improve outcome after SAH.

Background: Oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes are both lost in central nervous system injury and disease. Activated microglia may play a role in OPC and oligodendrocyte loss or replacement, but it is not clear how the responses of OPCs and oligodendrocytes to activated microglia differ.

OBJECTIVEThe ROSA device is a robotic stereotactic arm that uses a laser system to register the patient’s head or spine with MR or CT images. In this study, the authors analyze their experience with this system in pediatric neurosurgical applications and present selected cases that exemplify the usefulness of this system.METHODSThe authors reviewed all cases that utilized the ROSA system at their institution. Patient demographics, pathology, complications, electrode placement, laser ablation, and biopsy accuracy were analyzed. Patient disposition and condition at follow-up were also analyzed.RESULTSSeventeen patients underwent 23 procedures using the ROSA system. A total of 87 electroencephalography electrodes were placed, with 13% deviating more than 3 mm from target. Six patients underwent stereotactic needle biopsy, and 9 underwent laser interstitial thermotherapy (LITT). One patient who underwent LITT required a subsequent craniotomy for tumor resection. Another patient experienced an asymptomatic extraaxial hematoma that spontaneously resolved. No patient suffered neurological complications during follow-up. Follow-up from the last procedure averaged 180 days in epilepsy patients and 309 days in oncology patients.CONCLUSIONSThe precision, ease of use, and versatility of the ROSA system make it well suited for pediatric neurosurgical practice. Further work, including long-term analysis of results and cost-effectiveness, will help determine the utility of this system and if its applications can be expanded.

OBJECT The authors’ aim in this paper was to review the intraoperative use of epidural steroids in lumbar discectomy surgery with a focus on surgical complications. METHODS A comprehensive literature search was done using PubMed, MEDLINE, and the Cochrane Central Registry of Controlled Trials. Relevant papers were retrieved and analyzed. The authors performed a meta-analysis of all available data. Search terms included epidural, steroids, discectomy, lumbar disc surgery, herniated lumbar disc, methylprednisolone, and perioperative.The primary outcome was surgical complications such as wound infection or need for reoperation. Secondary outcomes were pain and postoperative narcotic usage. RESULTS Sixteen trials and 1 retrospective study (a total of 1933 patients) were eligible for inclusion in this study. In all studies, steroids were added epidurally over the nerve root before closure in cases, and control patients underwent discectomy alone. The mean age (42.7 years vs 42.4 years; RR 0.30 [95% CI −0.30 to 0.90], p = 0.32), overall complication rates (2.69% vs 1.18%; RR 1.94 [95% CI 0.72–5.26], p = 0.19), and infectious complication rates (0.94% vs 0.08%; RR 4.58 [95% CI 0.75–27.95], p = 0.10) were similar between the steroid group and control group, respectively. CONCLUSIONS There is good evidence that epidural steroids can decrease pain in the short term and decrease the usage of postoperative narcotics after lumbar spinal surgery for degenerative spinal disease. The authors’ results demonstrate a trend toward increased infection with epidural steroid use, but there was not a statistically significant difference. More studies are needed to validate the long-term risk/benefit ratio of epidural steroids in lumbar discectomy.

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The most important aspect of a preclinical study seeking to develop a novel therapy for neurological diseases is whether the therapy produces any clinically relevant functional recovery. For this purpose, neurobehavioral tests are commonly used to evaluate the neuroprotective efficacy of treatments in a wide array of cerebrovascular diseases and neurotrauma. Their use, however, has been limited in experimental subarachnoid hemorrhage studies. After several randomized, double-blinded, controlled clinical trials repeatedly failed to produce a benefit in functional outcome despite some improvement in angiographic vasospasm, more rigorous methods of neurobehavioral testing became critical to provide a more comprehensive evaluation of the functional efficacy of proposed treatments. While several subarachnoid hemorrhage studies have incorporated an array of neurobehavioral assays, a standardized methodology has not been agreed upon. Here, we review neurobehavioral tests for rodents and their potential application to subarachnoid hemorrhage studies. Developing a standardized neurobehavioral testing regimen in rodent studies of subarachnoid hemorrhage would allow for better comparison of results between laboratories and a better prediction of what interventions would produce functional benefits in humans.