Traumatic Central Nervous System Injury Research Articles

Phenotypic assays to identify agents that induce reactive gliosis: a counter-screen to prioritize compounds for preclinical animal studies.

Astrocyte phenotypes change in a process called reactive gliosis after traumatic central nervous system (CNS) injury. Astrogliosis is characterized by expansion of the glial fibrillary acidic protein (GFAP) cytoskeleton, adoption of stellate morphologies, and differential expression of some extracellular matrix molecules. The astrocytic response immediately after injury is beneficial, but in the chronic injury phase, reactive astrocytes produce inhibitory factors (i.e., chondroitin sulfate proteoglycans [CSPGs]) that limit the regrowth of injured axons. There are no drugs that promote axon regeneration or functional recovery after CNS trauma in humans. To develop novel therapeutics for the injured CNS, we screened various libraries in a phenotypic assay to identify compounds that promote neurite outgrowth. However, the effects these compounds have on astrocytes are unknown. Specifically, we were interested in whether compounds could alter astrocytes in a manner that mimics the glial reaction to injury. To test this hypothesis, we developed cell-based phenotypic bioassays to measure changes in (1) GFAP morphology/localization and (2) CSPG expression/immunoreactivity from primary astrocyte cultures. These assays were optimized for six-point dose-response experiments in 96-well plates. The GFAP morphology assay is suitable for counter-screening with a Z-factor of 0.44±0.03 (mean±standard error of the mean; N=3 biological replicates). The CSPG assay is reproducible and informative, but does not satisfy common metrics for a "screenable" assay. As proof of principle, we tested a small set of hit compounds from our neurite outgrowth bioassay and identified one that can enhance axon growth without exacerbating the deleterious characteristics of reactive gliosis.

Nestin-Positive Ependymal Cells Are Increased in the Human Spinal Cord after Traumatic Central Nervous System Injury

Endogenous neural progenitor cell niches have been identified in adult mammalian brain and spinal cord. Few studies have examined human spinal cord tissue for a neural progenitor cell response in disease or after injury. Here, we have compared cervical spinal cord sections from 14 individuals who died as a result of nontraumatic causes (controls) with 27 who died from injury with evidence of trauma to the central nervous system. Nestin immunoreactivity was used as a marker of neural progenitor cell response. There were significant increases in the percentage of ependymal cells that were nestin positive between controls and trauma cases. When sections from lumbar and thoracic spinal cord were available, nestin positivity was seen at all three spinal levels, suggesting that nestin reactivity is not simply a localized reaction to injury. There was a positive correlation between the percentage of ependymal cells that were nestin positive and post-injury survival time but not for age, postmortem delay, or glial fibrillary acidic protein (GFAP) immunoreactivity. No double-labelled nestin and GFAP cells were identified in the ependymal, subependymal, or parenchymal regions of the spinal cord. We need to further characterize this subset of ependymal cells to determine their role after injury, whether they are a population of neural progenitor cells with the potential for proliferation, migration, and differentiation for spinal cord repair, or whether they have other roles more in line with hypothalamic tanycytes, which they closely resemble.

Human ciliary neurotrophic factor–overexpressing stable bone marrow stromal cells in the treatment of a rat model of traumatic spinal cord injury

Background aimsTraumatic injury to the central nervous system (CNS) often causes motor dysfunctions. However, because of the CNS complexity and variability in the clinical presentations, efforts to repair damaged CNS tissue and restoring its functions are particularly demanding. On the other hand, recent progress in the regenerative therapy field have led to novel approaches for the treatment of traumatic CNS injury and renewed hopes to overcome the obstacles. It appears that the balance between neurite re-growth–inhibiting and neurite re-growth–inducing molecules determines the axonal re-growth fate. Neurotrophic factors can tilt this balance and indeed promote cell survival and axonal re-growth over neurodegeneration. One of the promising neurotrophic factors in this field is ciliary neurotrophic factor (CNTF). MethodsWe transfected rat bone marrow stromal cells with a mammalian expression vector–inserted human CNTF gene through the use of a non-viral method to prepare human CNTF-overexpressing stem cells under ex vivo conditions. We transplanted these modified cells to the rat model of spinal cord traumatic injury to explore functional recovery after contusion induction. ResultsOur data from immunocytochemistry and behavioral tests showed that such cells can act as a powerful potential approach to treat traumatic CNS injuries because these modified cells improved the behavioral test scores in the rat model of spinal cord injury. ConclusionsCNTF-overexpressing bone marrow stromal cells can ameliorate spinal cord traumatic injury and can be used in the treatment of traumatic CNS injuries in the near future.

Neuroprotective effects of nitidine against traumatic CNS injury via inhibiting microglia activation

Glial cell response to injury has been well documented in the pathogenesis after traumatic brain injury (TBI) and spinal cord injury (SCI). Although microglia, the resident macrophages in the central nervous system (CNS), are responsible for clearing debris and toxic substances, excessive activation of these cells will lead to exacerbated secondary damage by releasing a variety of inflammatory and cytotoxic mediators and ultimately influence the subsequent repair after CNS injury. In fact, inhibition of microgliosis represents a therapeutic strategy for CNS trauma. We here showed that nitidine, a benzophenanthridine alkaloid, restricted reactive microgliosis and promoted CNS repair after traumatic injury. Nitidine was shown to prevent cultured microglia from LPS-induced reactive activation by regulation of ERK and NF-κB signaling pathway. Furthermore, the nitidine-mediated inhibition of microgliosis was also shown in injured brain and spinal cord, which significantly increased neuronal survival and decreased neural tissue damage after injury. Importantly, behavioral analysis revealed that nitidine-treated mice with SCI had improved functional recovery as assessed by Basso Mouse Scale and swimming test. Together, these findings indicated that nitidine increased CNS tissue sparing and improved functional recovery by attenuating reactive microgliosis, suggestive of the potential therapeutic benefit for CNS injury.

Radiological features of pneumonia in children with hypoxic-ischemic and traumatic CNS injuries

The most common complication of lung disease in children with hypoxic-ischemic and traumatic lesions of the central nervous system is pneumonia. Methods. To clarify radiological features of pneumonia in children with hypoxic-ischemic and traumatic lesions of the central nervous system (CNS) were studied chest X-ray (CXR) of 127 children (71 boys and 56 girls) with a diagnosis of hypoxic-ischemic and traumatic CNS lesion. Results. In the examined patients usually observed focal (63,8±3,5 %) and segmental pneumonia (36,8±4,4 %), that has its characteristic features on chest X-rays. Premature infants with hypoxic-ischemic lesions of the central nervous system has higher frequency of pneumonia (61,4 5,9 %) then term children’s with traumatic lesions of the central nervous system – 38,6±4,5 % of cases. Conclusions. X-ray method of research is leading in diagnostics of pneumonia in children with hypoxic-ischemic and traumatic CNS lesion. It allows to establishing the nature of the pathological process, its features, degree distribution and dynamics and effectiveness of the treatment. In premature infants dominated focal pneumonia, in term children – segmental. Development of segmental pneumonia on the background of aspiration syndrome is more characteristic for mature infants

A perspective on the role of class III semaphorin signaling in central nervous system trauma.

Traumatic injury of the central nervous system (CNS) has severe impact on the patients’ quality of life and initiates many molecular and cellular changes at the site of insult. Traumatic CNS injury results in direct damage of the axons of CNS neurons, loss of myelin sheaths, destruction of the surrounding vascular architecture and initiation of an immune response. Class III semaphorins (SEMA3s) are present in the neural scar and influence a wide range of molecules and cell types in and surrounding the injured tissue. SEMA3s and their receptors, neuropilins (NRPs) and plexins (PLXNs) were initially studied because of their involvement in repulsive axon guidance. To date, SEMA3 signaling is recognized to be of crucial importance for re-vascularization, the immune response and remyelination. The purpose of this review is to summarize and discuss how SEMA3s modulate these processes that are all crucial components of the tissue response to injury. Most of the functions for SEMA3s are achieved through their binding partners NRPs, which are also co-receptors for a variety of other molecules implicated in the above processes. The most notable ligands are members of the vascular endothelial growth factor (VEGF) family and the transforming growth factor family. Therefore, a second aim is to highlight the overlapping or competing signaling pathways that are mediated through NRPs in the same processes. In conclusion, we show that the role of SEMA3s goes beyond inhibiting axonal regeneration, since they are also critical modulators of re-vascularization, the immune response and re-myelination.

Complications of trauma patients admitted to the ICU in level I academic trauma centers in the United States.

Background. The aims of this study were to evaluate the complications that occur after trauma and the characteristics of individuals who develop complications, to identify potential risk factors that increase their incidence, and finally to investigate the relationship between complications and mortality. Methods. We did a population-based retrospective study of trauma patients admitted to ICUs of a level I trauma center. Logistic regression analyses were performed to determine independent predictors for complications. Results. Of the 11,064 patients studied, 3,451 trauma patients developed complications (31.2%). Complications occurred significantly more in younger male patients. Length of stay was correlated with the number of complications (R = 0.435, P < 0.0001). The overall death rate did not differ between patients with or without complications. The adjusted odds ratio (OR) of developing complication for patients over age 75 versus young adults was 0.7 (P < 0.0001). Among males, traumatic central nervous system (CNS) injury was an important predictor for complications (adjusted OR 1.24). Conclusions. Complications after trauma were found to be associated with age, gender, and traumatic CNS injury. Although these are not modifiable factors, they may identify subjects at high risk for the development of complications, allowing for preemptive strategies for prevention.

Cell-Based Therapeutic Strategies in Multiple Sclerosis

Multiple sclerosis (MS) is an immune-mediated disease in which acute inflammatory demyelination leads to axonal injury and neurodegeneration, and is manifested clinically by relapsing–remitting neurological deficits superimposed on chronic accumulation of disability. MS treatments are largely immunomodulatory with little, if any, effect on neurodegeneration. Mesenchymal stem cells MSCs) are pluripotent cells derived from adult tissues with intrinsic anti-inflammatory and repair-promoting properties. They cross the blood–brain barrier and target perivascular spaces, which are the sites of inflammatory cell infiltration in MS.In vitro, MSCs can be purified and expanded, labelled for post-transplant tracking and be manipulated to express surface receptors or neurotrophic factors for central nervous system (CNS) targeting or neuroprotection, respectively. Animal models of MS, traumatic CNS injury and neurodegenerative diseases demonstrate clinical and pathological benefits following MSC transplantation. Potentially, MSCs can be used to treat MS patients at various disease stages, which is the current focus of ongoing phase I/II clinical trials at multiple centres.

Membrane resealing as a promising strategy for early treatment of neurotrauma

Membrane resealing as a promising strategy for early treatment of neurotrauma

Role of nuclear factor kappa B in central nervous system regeneration.

Activation of nuclear factor kappa B (NF-κB) is a hallmark of various central nervous system (CNS) pathologies. Neuron-specific inhibition of its transcriptional activator subunit RelA, also referred to as p65, promotes neuronal survival under a range of conditions, i.e., for ischemic or excitotoxic insults. In macro- and microglial cells, post-lesional activation of NF-κB triggers a growth-permissive program which contributes to neural tissue inflammation, scar formation, and the expression of axonal growth inhibitors. Intriguingly, inhibition of such inducible NF-κB in the neuro-glial compartment, i.e., by genetic ablation of RelA or overexpression of a transdominant negative mutant of its upstream regulator IκBα, significantly enhances functional recovery and promotes axonal regeneration in the mature CNS. By contrast, depletion of the NF-κB subunit p50, which lacks transcriptional activator function and acts as a transcriptional repressor on its own, causes precocious neuronal loss and exacerbates axonal degeneration in the lesioned brain. Collectively, the data imply that NF-κB orchestrates a multicellular program in which κB-dependent gene expression establishes a growth-repulsive terrain within the post-lesioned brain that limits structural regeneration of neuronal circuits. Considering these subunit-specific functions, interference with the NF-κB pathway might hold clinical potentials to improve functional restoration following traumatic CNS injury

Phagocytic Removal of Neuronal Debris by Olfactory Ensheathing Cells Enhances Neuronal Survival and Neurite Outgrowth via p38MAPK Activity

Compelling evidence from animal models and clinical studies suggest that transplantation of olfactory ensheathing cells (OECs), specialized glia in the olfactory system, combined with specific training may be therapeutically useful in the central nervous system (CNS) injuries and neurodegenerative diseases. The unique function of OECs could mainly attribute to both production of cell adhesion molecules and secretion of growth factors in OECs, which support neuron survival and neurite outgrowth. However, little is known about whether engulfment of neuronal degenerative debris by OECs also equally contributes to neuronal survival and neurite outgrowth. Furthermore, the molecular mechanisms responsible for neuronal degenerative corpses' removal remain elusive. Here, we used an in vitro model of primary culture of spinal cord neurons to investigate the effect of engulfment of degenerative neuron debris by OECs on neuronal survival and neurite outgrowth and the possible molecular mechanisms. Our results showed that OECs can engulf an amount of degenerated neuron debris, and this phagocytosis can make a substantial contribution to neuron growth, as demonstrated by increased number of neurons with longer neurite length and richer neurite branches when compared with the combination of neuron debris and OEC conditioned medium (OECCM). Moreover, p38 mitogen-activated protein kinase (p38MAPK) signaling pathway may mediate the OEC engulfment of debris because the p38MAPK-specific inhibitor, SB203580, can abrogate all the positive effects of OECs, including clearance of degenerated neuron debris and generation of bioactive molecules, indicating that p38MAPK is required for the process of phagocytosis of the neuron debris. In addition, the OEC phagocytic activity had no influence on its generation of bioactive molecules. Therefore, these findings provide new insight into further investigations on the OEC role in the repair of traumatic CNS injury and neurodegenerative diseases.

127. Decreased functional recovery after SCI in aged mice corresponds with impaired IL-4Rα upregulation on microglia and reduced IL-4-dependent repair

Activated microglia from aged mice are less responsive to anti-inflammatory signals. Indeed, our lab showed that activated microglia from aged mice have impaired upregulation of the receptor for the anti-inflammatory cytokine, interleukin (IL)-4. Impaired upregulation of the IL-4 receptor (IL-4R α ) resulted in reduced sensitivity to the M2 promoting effects of IL-4 ex vivo (i.e., high inducible nitric oxide synthase; low arginase). We hypothesize that this failure to induce IL-4R α after an inflammatory challenge sensitizes aged mice to a traumatic central nervous system (CNS) injury in which IL-4-dependent repair relies on increased IL-4R α expression. Here we show that after a spinal cord injury (SCI), microglia from adult, but not aged, mice upregulated surface expression of IL-4R α . Impaired IL-4R α upregulation corresponded with reduced functional recovery in aged mice and reduced arginase expression in the spinal cord. Thus, we predict that impaired IL-4R α upregulation after SCI results in decreased arginase-associated repair including reduced axonal growth. In support of this idea, we used an intracerebroventricular injection model to show that IL-4-mediated arginase expression in microglia is dependent on inflammatory-induced IL-4R α upregulation. Moreover, in dorsal root ganglion cultures, IL-4-induced neurite growth was only noted in the presence activated microglia (high IL-4R α ). Together, these results indicate that impaired IL-4R α expression by aged mice after SCI likely leads to reduced IL-4-dependent reparative processes resulting in reduced functional recovery.

Palmitoylethanolamide in Homeostatic and Traumatic Central Nervous System Injuries

The role of palmitoylethanolamide (PEA) in the regulation of complex systems involved in the inflammatory response, pruritus, neurogenic and neuropathic pain is well understood. Growing evidence indicates that this Nacylethanolamine also exerts neuroprotective effects within the central nervous system (CNS), i.e. in spinal cord and traumatic brain injuries and in age-related pathological processes. PEA is abundant in the CNS, and is produced by glial cells. Several studies show that administering PEA during the first few hours after injury significantly limits CNS damage, reduces loss of neuronal tissue and improves functional recovery. PEA appears to exert its protective effect by decreasing the development of cerebral edema, down-regulating the inflammatory cascade, and limiting cellular necrosis and apoptosis. All these are plausible mechanisms of neuroprotection. This review provides an overview of current knowledge of PEA effect on glial functions in the brain and how targeting glial-specific pathways might ultimately impact the development of therapies for clinical management of neurodegenerative disorders. The diverse signaling mechanisms are also summarized.

Temporal Changes in Cell Marker Expression and Cellular Infiltration in a Controlled Cortical Impact Model in Adult Male C57BL/6 Mice

BackgroundTraumatic injury to the central nervous system (CNS) triggers a robust inflammatory response that leads to axonal damage and secondary degeneration of spared tissue. In contrast, some immune responses have neuroprotective effects. However, detailed information regarding the dynamics of immune responses after traumatic CNS injury is still unavailable.MethodsIn the present study, changes in the immune cells present in the injured brain, spleen, and cervical lymph nodes (CLNs), which are draining lymphatic organs from the CNS, were analyzed after controlled cortical impact (CCI) by flow cytometry and immunohistochemistry.ResultsThe number of neutrophils and macrophages that infiltrated the injured brain immediately increased 1 d post-injury and declined rapidly thereafter. In the injured brain, resident microglia showed a bimodal increase during the first week and in the chronic phase (≥3 weeks) after injury. Increase in the Iba-1+ microglia/macrophages was observed around the injured site. Morphologic analysis showed that Iba-1+ cells were round at 1 week, whereas those at 3 weeks were more ramified. Furthermore, CD86+/CD11b+ M1-like microglia increased at 4 weeks after CCI, whereas CD206+/CD11b+ M2-like microglia increased at 1 week. These results suggest that different subsets of microglia increased in the acute and chronic phases after CCI. Dendritic cells and T cells increased transiently within 1 week in the injured brain. In the CLNs and the spleen, T cells showed dynamic changes after CCI. In particular, the alteration in the number of T cells in the CLNs showed a similar pattern, with a 1-week delay, to that of microglia in the injured brain.ConclusionThe data from this study provide useful information on the dynamics of immune cells in CNS injuries.

In vitro beneficial activation of microglial cells by mechanically-injured astrocytes enhances the synthesis and secretion of BDNF through p38MAPK

It has long been promulgated that microglial cells serve beneficial roles in the central nervous system (CNS). The beneficial role of microglial cells is considered to be linked with microglial activation and consequent up-regulation of various trophic factors. However, what triggers microglial activation and consequent elevated level of trophic factors, especially brain-derived neurotrophic factor (BDNF), following traumatic CNS injury has become a crucial but elusive issue. Furthermore, an effort still remains in understanding of the cellular and molecular mechanisms underlying the endogenous neuroprotection of activated microglial cells. In this study, we demonstrated that mechanically-injured astrocyte conditioned medium (ACM) could provoke beneficial activation of microglial cells and thus promote the transcription, synthesis and release of BDNF in cultured microglial cells. The microglia-derived BDNF can exerted a demonstrable biological role in promoting neurite outgrowth and intimate terminal contacts of dorsal root ganglion (DRG) neurons co-cultured with microglial cells. Moreover, ACM induced remarkable p38MAPK phosphorylation in cultured microglial cells that preceded the burst of BDNF. Activating p38-MAPK by anisomycin resulted in salutary effects similar to those seen with ACM, whereas specific inhibition of the p38MAPK by SB203580 abrogated all the positive effects of ACM, including BDNF promotion and subsequent neurite outgrowth of DRG neurite outgrowth of DRG neurons and their intimate terminal contacts with microglial cells. Together, our results indicated that the neuroprotection of the microglial source is mainly caused by micro-environmental soluble molecules released from injured astrocytes, and ACM-induced BDNF production and release from microglial cells may be mediated through p38-MAPK signaling pathway. Therefore, these findings may lay a foundation to further investigations on the microglial beneficial activation role in the repair of traumatic CNS injury and neurodegenerative diseases.

Gene Therapy for Traumatic Central Nervous System Injury and Stroke Using an Engineered Zinc Finger Protein that Upregulates VEGF-A

Recent studies have identified anti-apoptotic functions for vascular endothelial growth factor (VEGF) in the central nervous system (CNS). However, VEGF therapy has been hampered by a tendency to promote vascular permeability, edema, and inflammation. Recently, engineered zinc finger proteins (ZFPs) that upregulate multiple forms of VEGF in their natural biological ratios, have been developed to overcome these negative side effects. We used retinal trauma and ischemia models, and a cortical pial strip ischemia model to determine if VEGF upregulating ZFPs are neuroprotective in the adult CNS. Optic nerve transection and ophthalmic artery ligation lead to the apoptotic degeneration of retinal ganglion cells (RGCs) and are, respectively, two highly reproducible models for CNS trauma or ischemia. Adeno-associated vectors (AAV) vectors encoding VEGF-ZFPs (AAV-VEGF-ZFP) significantly increased RGC survival by ∼twofold at 14 days after optic nerve transection or ophthalmic artery ligation. Furthermore, AAV-VEGF-ZFP enhanced recovery of the pupillary light reflex. RECA-1 immunostaining demonstrated no appreciable differences between retinas treated with AAV-VEGF-ZFP and controls, suggesting that AAV-VEGF-ZFP treatment did not affect retinal vasculature. Following pial strip of the forelimb motor cortex, brains treated with an adenovirus encoding VEGF ZFPs (AdV-ZFP) showed higher neuronal survival, accelerated wound contraction, and reduced lesion volume between 1 and 6 weeks after injury. Behavioral testing using the cylinder test for vertical exploration showed that AdV-VEGF-ZFP treatment enhanced contralateral forelimb function within the first 2 weeks after injury. Our results indicate that VEGF ZFP therapy is neuroprotective following traumatic injury or stroke in the adult mammalian CNS.

Reduction in expression of the astrocyte glutamate transporter, GLT1, worsens functional and histological outcomes following traumatic spinal cord injury

The astrocyte glutamate transporter, GLT1, is responsible for the vast majority of glutamate uptake in the adult central nervous system (CNS), thereby regulating extracellular glutamate homeostasis and preventing excitotoxicity. Glutamate dysregulation plays a central role in outcome following traumatic spinal cord injury (SCI). To determine the role of GLT1 in secondary cell loss following SCI, mice heterozygous for the GLT1 astrocyte glutamate transporter (GLT1+/-) and wild-type mice received thoracic crush SCI. Compared with wild-type controls, GLT1+/- mice had an attenuated recovery in hindlimb motor function, increased lesion size, and decreased tissue sparing. GLT1+/- mice showed a decrease in intraspinal GLT1 protein and functional glutamate uptake compared with wild-type mice, accompanied by increased apoptosis and neuronal loss following crush injury. These results suggest that astrocyte GLT1 plays a role in limiting secondary cell death following SCI, and also show that compromise of key astrocyte functions has significant effects on outcome following traumatic CNS injury. These findings also suggest that increasing intraspinal GLT1 expression may represent a therapeutically relevant target for SCI treatment.

MicroRNA in central nervous system trauma and degenerative disorders

MicroRNAs (miRNAs) are a novel class of small noncoding RNAs that negatively regulate gene expression at the posttranscriptional level by binding to the 3'-untranslated region of target mRNAs leading to their translational inhibition or sometimes degradation. MiRNAs are predicted to control the activity of at least 20-30% of human protein-coding genes. Recent studies have demonstrated that miRNAs are highly expressed in the central nervous system (CNS) including the brain and spinal cord. Although we are currently in the initial stages of understanding how this novel class of gene regulators is involved in neurological biological functions, a growing body of exciting evidence suggests that miRNAs are important regulators of diverse biological processes such as cell differentiation, growth, proliferation, and apoptosis. Moreover, miRNAs are key modulators of both CNS development and plasticity. Some miRNAs have been implicated in several neurological disorders such as traumatic CNS injuries and neurodegenerative diseases. Recently, several studies suggested the possibility of miRNA involvement in neurodegeneration. Identifying the roles of miRNAs and their target genes and signaling pathways in neurological disorders will be critical for future research. miRNAs may represent a new layer of regulators for neurobiology and a novel class of therapeutic targets for neurological diseases.

Therapeutic potential of melatonin in traumatic central nervous system injury

A vast literature extolling the benefits of melatonin has accumulated during the past four decades. Melatonin was previously considered of importance to seasonal reproduction and circadian rhythmicity. Currently, it appears to be a versatile anti-oxidative and anti-nitrosative agent, a molecule with immunomodulatory actions and profound oncostatic activity, and also to play a role as a potent neuroprotectant. Nowadays, melatonin is sold as a dietary supplement with differential availability as an over-the-counter aid in different countries. There is a widespread agreement that melatonin is nontoxic and safe considering its frequent, long-term usage by humans at both physiological and pharmacological doses with no reported side effects. Endeavors toward a designated drug status for melatonin may be enormously rewarding in clinics for treatment of several forms of neurotrauma where effective pharmacological intervention has not yet been attained. This mini review consolidates the data regarding the efficacy of melatonin as an unique neuroprotective agent in traumatic central nervous system (CNS) injuries. Well-documented actions of melatonin in combating traumatic CNS damage are compiled from various clinical and experimental studies. Research on traumatic brain injury and ischemia/reperfusion are briefly outlined here as they have been recently reviewed elsewhere, whereas the studies on different animal models of the experimental spinal cord injury have been extensively covered in this mini review for the first time.

Intrathecal Baclofen Therapy to Reduce Spacticity in Two Patients with Traumatic Central Nervous System Injury

Spasticity is a common sequela in patients with spinal cord injury (SCI) or traumatic brain injury (TBI). Conventional oral baclofen therapy in large doses may induce gastrointestinal discomfort and neuropsychiatric symptoms. Intrathecal baclofen (ITB) is a relatively new modality for treating spasticity of spinal cord origin. Herein, we present our experience with ITB therapy for treatment of SCI- and TBI-related spasticity. Case 1 involves a 21-year-old man with SCI at the C3-C4 region accompanied by a traumatic herniated intervertebral disc, resulting in incomplete tetraplegia. Case 2 involves a 19-year-old man with a localized brain contusion and acute subdural hematoma in the left frontal-temporal-parietal lobe. Both patients underwent ITB implantation after preoperative and ITB screening 28 months and 29 months, respectively to treat severe spasticity. Functional independent measure scores and mean modified Ashworth scores were calculated preoperatively and postoperatively in both patients to evaluate outcome of ITB therapy. Overall, both patients exhibited a good response. Mean modified Ashworth scores decreased soon after ITB implantation and adequate dosage adjustment in both patients. Functional independent scores improved gradually during the follow-up periods. There were no complications, and no overdose or withdrawal symptoms at 3-month postoperative follow-up in case 1 and at 7-month postoperative follow-up in case 2. ITB therapy is effective in reducing spasticity in patients with SCI and in patients with TBI.