Neurotherapeutic Interventions Research Articles

Biocompatible triboelectric energy generators (BT-TENGs) for energy harvesting and healthcare applications.

Electronic waste (e-waste) has become a significant environmental and societal challenge, necessitating the development of sustainable alternatives. Biocompatible and biodegradable electronic devices offer a promising solution to mitigate e-waste and provide viable alternatives for various applications, including triboelectric nanogenerators (TENGs). This review provides a comprehensive overview of recent advancements in biocompatible, biodegradable, and implantable TENGs, emphasizing their potential as energy scavengers for healthcare devices. The review delves into the fabrication processes of self-powered TENGs using natural biopolymers, highlighting their biodegradability and compatibility with biological tissues. It further explores the biomedical applications of ultrasound-based TENGs, including their roles in wound healing and energy generation. Notably, the review presents the novel application of TENGs for vagus nerve stimulation, demonstrating their potential in neurotherapeutic interventions. Key findings include the identification of optimal biopolymer materials for TENG fabrication, the effectiveness of TENGs in energy harvesting from physiological movements, and the potential of these devices in regenerative medicine. Finally, the review discusses the challenges in scaling up the production of implantable TENGs from biomaterials, addressing issues such as mechanical stability, long-term biocompatibility, and integration with existing medical devices, outlining future research opportunities to enhance their performance and broaden their applications in the biomedical field.

Dramatic Reanimation and Spontaneous Re-Canalization of a Fourth Ventricular Hemorrhage: “REVIVE” Phenomenon

Background Intraventricular hemorrhage is a calamitous type of stroke where bleeding into the ventricular system can be defined as: primary, if confined within the ventricles; or secondary, due to intracerebral hemorrhage extending from adjacent parenchyma. Intraventricular blood clot can lead to secondary insult and inflammatory responses that culminates in hydrocephalus as the most common cause of death. Purpose THerein, we report a patient with a high modified Graeb scale and low Glasgow coma scale. She spontaneously recanalized her fourth ventricle, decompressed her reticular activating system with remarkable spontaneous bilateral eye opening, and a consequently experienced a halfway drop in her mGS. Results This is the first reported case of a spontaneous recanalization of 4th ventricle obstruction secondary to IVH without intervention and subsequent dramatic neurological improvement. We believe that the apixaban primarily preserved the liquid state of hemorrhage and her presumed elevated ICP was sufficient to push out the liquified blood in the 4th ventricle into the upper spinal canal , recanalizing the 4th ventricle by continuously creating downward CSF pressure waves. Given the RAS location around the 4th ventricle, we hypothesize spontaneous decompression from the clot lysis triggered the RAS activation with sudden arousal manifested as spontaneous bilateral eyes opening. Hence, we refer to this as the reticular activating system reactivation after ventricular hemorrhage evacuation, or simply the “REVIVE” phenomenon. Conclusion This dramatic improvement from coma to awake state is worthy of recognition for future neurotherapeutic interventions.

Microdosing of a kappa opioid receptor agonist within proximal nucleus accumbens shell microstructures revealing opposing behavioral outcomes

Targeted intracranial delivery of molecularly-specific therapies within intricate brain structures poses a formidable challenge due to the heterogeneity of neuronal phenotypes and functions. Here we report the use of an implantable, miniaturized neural drug delivery system permitting dynamic adjustment of pharmacotherapies. Specifically, we exploit the spatial accuracy afforded by this method for targeting modulation of neuronal microstructures. Kappa opioid receptors (KOR) within the dorsal medial nucleus accumbens shell (NASh) are selectively activated through micro infusions of the KOR agonist, U-50488. Remarkably, we demonstrate that micro infusions of U-50488 into the dorsal NASh induces reward-like conditioned place preferences, whereas a mere 1 mm shift ventrally results in conditioned place aversions. The striking precision afforded by this method may prove useful in other neurotherapeutic interventions.

Comparative Evaluation of the Ameliorating Effects of Some Natural Products as Neurotherapeutic Interventions for a Neurodegenerative Disorder in Status Epilepticus Model

Comparative Evaluation of the Ameliorating Effects of Some Natural Products as Neurotherapeutic Interventions for a Neurodegenerative Disorder in Status Epilepticus Model

Comparative Neuroprotective Potential of Nanoformulated and Free Resveratrol Against Cuprizone-Induced Demyelination in Rats.

Demyelination is a frequent yet crippling neurological disease associated with multiple sclerosis (MS). The cuprizone (CZ) model, which causes demyelination through oxidative stress and neuroinflammation, is a popular tool used by researchers to examine this process. The polyphenol resveratrol (RESV) has become a promising neuroprotective agent in seeking for efficient therapies. In a rat model given CZ, we created and examined iron oxide nanoparticles (IONPs) loaded with RESV (IONP-RESV) to see how effective they were as a therapeutic agent against free RESV. According to molecular mechanisms, exposure to CZ resulted in a marked downregulation of myelin proteolipid protein (PLP) expression and an overexpression of the inflammatory markers tumor necrosis factor-α (TNF-α) and S100β, which are indicators of demyelination and neuroinflammation. It is remarkable that these CZ-induced alterations could be reversed by therapy with either RESV or IONP-RESV. Interestingly, IONP-RESV showed even stronger anti-inflammatory activity, as shown by a more noticeable downregulation of TNF-α and S100β expression. These results were confirmed by histopathological examination of the cerebral cortices. Our findings support the better neuroprotective benefits of RESV-loaded IONPs over free RESV in reducing demyelination and neuroinflammation brought on by CZ. Owing to their pro-remyelinating, anti-inflammatory, and antioxidant properties, RESV-loaded IONPs show promise as a neurotherapeutic intervention in the future for neurological diseases such as multiple sclerosis.

Protein Kinase C (PKC) in Neurological Health: Implications for Alzheimer's Disease and Chronic Alcohol Consumption.

Protein kinase C (PKC) is a diverse enzyme family crucial for cell signalling in various organs. Its dysregulation is linked to numerous diseases, including cancer, cardiovascular disorders, and neurological problems. In the brain, PKC plays pivotal roles in synaptic plasticity, learning, memory, and neuronal survival. Specifically, PKC's involvement in Alzheimer's Disease (AD) pathogenesis is of significant interest. The dysregulation of PKC signalling has been linked to neurological disorders, including AD. This review elucidates PKC's pivotal role in neurological health, particularly its implications in AD pathogenesis and chronic alcohol addiction. AD, characterised by neurodegeneration, implicates PKC dysregulation in synaptic dysfunction and cognitive decline. Conversely, chronic alcohol consumption elicits neural adaptations intertwined with PKC signalling, exacerbating addictive behaviours. By unravelling PKC's involvement in these afflictions, potential therapeutic avenues emerge, offering promise for ameliorating their debilitating effects. This review navigates the complex interplay between PKC, AD pathology, and alcohol addiction, illuminating pathways for future neurotherapeutic interventions.

The Interplay of Sports and Nutrition in Neurological Health and Recovery.

This comprehensive review explores the dynamic relationship between sports, nutrition, and neurological health. Focusing on recent clinical advancements, it examines how physical activity and dietary practices influence the prevention, treatment, and rehabilitation of various neurological conditions. The review highlights the role of neuroimaging in understanding these interactions, discusses emerging technologies in neurotherapeutic interventions, and evaluates the efficacy of sports and nutritional strategies in enhancing neurological recovery. This synthesis of current knowledge aims to provide a deeper understanding of how lifestyle factors can be integrated into clinical practices to improve neurological outcomes.

P30: Neuro-therapeutic play with Asian older adults: a qualitative analysis.

Neuro-therapeutic intervention joins play for older adults with and without cognitive decline in Asia. During the Covid-19 outbreak, older adults report an increased isolation and increased risk for cognitive decline and medical complications than younger populations. It is therefore reasonable to implement creative nonpharmacological interventions to satisfy older adults psycho-social needs while maintaining their cognitive functioning without being burdened with healthcare costs. In this interventional study, a group of 60 older adults aged 60 years old and older participated in sand tray activity for six weeks. Participants were interviewed for their experiences with six sand tray activities under social distance restrictions in Taiwan. Thematic analysis techniques are applied to examine the interviewing data to identify comment themes across participants. The qualitative results show that social connection is the need of older adults during the pandemic, that neuro-therapeutic play satisfies older adults’ emotional needs, and that sand tray activity offers an opportunity for older adults to exercise their brain. Implications are discussed.

'Advocacy groups are the connectors': Experiences and contributions of rare disease patient organization leaders in advanced neurotherapeutics.

Biomedical progress has facilitated breakthrough advanced neurotherapeutic interventions, whose potential to improve outcomes in rare neurological diseases has increased hope among people with lived experiences and their carers. Nevertheless, gene, somatic celland other advanced neurotherapeutic interventions carry significant risks. Rare disease patient organizations (RDPOs) may enhance patient experiences, inform expectationsand promote health literacy. However, their perspectives are understudied in paediatric neurology. If advanced neurotherapeutics is to optimize RDPO contributions, it demands further insights into their roles, interactionsand support needs. We used a mixed-methodology approach, interviewing 20 RDPO leaders representing paediatric rare neurological diseasesand following them up with two online surveys featuring closed and open-ended questions on advanced neurotherapeutics (19/20) and negative mood states (17/20). Qualitative and quantitative data were analysed using thematic discourse analysis and basic descriptive statistics, respectively. Leaders perceived their roles to be targeted at educational provision (20/20), community preparation for advanced neurotherapeutic clinical trials (19/20), information simplification (19/20)and focused research pursuits (20/20). Although most leaders perceived the benefits of collaboration between stakeholders, some cited challenges around collaborative engagement under the following subthemes: conflicts of interest, competitionand logistical difficulties. Regarding neurotherapeutics, RDPO leaders identified support needs centred on information provision, valuing access to clinician experts and highlighting a demand for co-developed, centralized, high-leveland understandable, resources that may improve information exchange. Leaders perceived a need for psychosocial support within themselves and their communities, proposing that this would facilitate informed decision-making, reduce associated psychological vulnerabilitiesand maintain hope throughout neurotherapeutic development. This study provides insights into RDPO research activities, interactionsand resource needs. It reveals a demand for collaboration guidelines, central information resourcesand psychosocial supports that may address unmet needs and assist RDPOs in their advocacy. In this study, RDPO leaders were interviewed and surveyed to examine their perspectives and roles in advanced neurotherapeutic development. Some participants sent researchers postinterview clarification emails regarding their responses to questions.

The Armadillo as a Model for Leprosy Nerve Function Impairment: Preventative and Therapeutic Interventions.

Mycobacterium leprae infection of peripheral nerves and the subsequent nerve function impairment (NFI), especially in response to reactional episodes, are hallmarks of leprosy. Improved treatments for M. leprae-induced nerve injury are needed, as most if not all of the disability and stigma associated with leprosy arises from the direct or indirect effects of NFI. Nine-banded armadillos (Dasypus novemcinctus), like humans, exhibit the full clinical spectrum of leprosy and extensive involvement of the peripheral nerves. In this study, state-of-the-art technology was used to compare nerve function between uninfected and M. leprae-infected armadillos. Motor nerve conduction velocity (MNCV) and compound muscle action potential (cMAP), which measure changes in the rate of impulse conduction velocity and amplitude, revealed a progression of impairment that was directly correlated with the duration of M. leprae infection and enabled development of an objective nerve impairment scoring system. Ultrasonography accompanied by color Doppler imaging detected enlargement of the M. leprae-infected nerves and increased vascularity, possibly due to inflammation. Assessment of epidermal nerve fiber density (ENFD), which shows a length-dependent innervation in armadillos that is similar to humans, identified small fiber degeneration early after M. leprae infection. Staining for neuromuscular junction (NMJ) integrity, which is an indicator of signal transduction efficiency into skeletal muscle, discerned a markedly lower number and structural integrity of NMJ in M. leprae-infected armadillo footpads. These tools for assessing nerve injury were used to monitor the effects of intervention therapy. Two potential neuro-protective drugs, ethoxyquin (EQ) and 4-aminopyridine (4-AP), were tested for their ability to ameliorate peripheral nerve injury in M. leprae-infected armadillos. 4-AP treatment improved MNCV, cMAP, and EFND compared to untreated animals, while EQ had less effect. These results support the armadillo as a model for M. leprae-induced peripheral nerve injury that can provide insights toward the understanding of NFI progression and contribute to the preclinical investigation of the safety and efficacy of neuro-preventive and neuro-therapeutic interventions for leprosy.

Neurologic outcome after fetal inflammatory response syndrome: Trimester-specific considerations

Clinical signs and neuroimaging patterns associated with the fetal inflammatory response syndrome (FIRS) worsen or mimic the clinical repertoire after intrapartum hypoxic-ischemic encephalopathy (HIE) during labor and/or parturition. Diagnostic considerations expressed as neonatal encephalopathy (NE) must consider chronic as well as acute factors associated with FIRS. Trimester-specific factors adversely alter the interactions of the maternal/placental/fetal (MPF) triad and influence the postnatal phenotype of FIRS. Anticipatory guidance for families by clinicians caring for survivors with FIRS, as well as researchers, must consider acute and chronic effects that influence neurologic outcome. Novel neurotherapeutic interventions must include prenatal preventive as well as peripartum/postnatal rescue and repair strategies to effectively reduce the presence and severity of sequelae from FIRS.

Tannic Acid Provides Neuroprotective Effects Against Traumatic Brain Injury Through the PGC-1α/Nrf2/HO-1 Pathway.

The present research was conducted to elucidate a possible molecular mechanism related to neuromodulatory effects of tannic acid (TA) supplementation against traumatic brain injury (TBI) in a rodent model. Oxidative damage and neuroinflammation play a critical role in TBI and lead to behavioral alterations and neuronal dysfunction and death. These changes suggest a potential avenue in neurotherapeutic intervention. The aim of the present study was to investigate the neuroprotective effects of TA and potential mechanism of these effects in a controlled cortical impact injury model of TBI in Wistar rats that were treated with TA (50mg/kg body weight. i.p.) before 30min and 6 and 18h after TBI. TBI-induced rats were examined after 24h for behavioral dysfunction, Nissl stain, lipid peroxidation rate, glutathione level, activities of antioxidant enzymes (catalase, glutathione S-transferase, glutathione peroxidase, and superoxide dismutase), the expression level of 4-hydroxynonenal, pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-1 beta, as well as brain edema and immunoreactivity of glial fibrillary acidic protein. Results indicated that TA supplementation significantly modulated above mentioned alterations. Moreover, TA treatment effectively upregulated the protein expression of peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α) and nuclear factor-E2-related factor-2 (Nrf2) as well as mitochondrial transcription factor A and heme oxygenase-1 (HO-1) following TBI. Overall, our results suggest that TA effectively ameliorates the behavioral alterations, oxidative damage, mitochondrial impairment, and inflammation against TBI that may be attributed to activation of PGC-1α/Nrf-2/HO-1 signaling pathway.

Chapter 1 - Fetal neurology: Principles and practice with a life-course perspective

Clinical service, educational, and research components of a fetal/neonatal neurology program are anchored by the disciplines of developmental origins of health and disease and life-course science as programmatic principles. Prenatal participation provides perspectives on maternal, fetal, and placental contributions to health or disease for fetal and subsequent neonatal neurology consultations. This program also provides an early-life diagnostic perspective for neurologic specialties concerned with brain health and disease throughout childhood and adulthood. Animal models and birth cohort studies have demonstrated how the science of epigenetics helps to understand gene-environment interactions to better predict brain health or disease. Fetal neurology consultations provide important diagnostic contributions during critical or sensitive periods of brain development when future neurotherapeutic interventions will maximize adaptive neuroplasticity. Age-specific normative neuroinformatics databases that employ computer-based strategies to integrate clinical/demographic, neuroimaging, neurophysiologic, and genetic datasets will more accurately identify either symptomatic patients or those at risk for brain disorders who would benefit from preventive, rescue, or reparative treatment choices throughout the life span.

Basic fibroblast growth factor enhances cell proliferation in the dentate gyrus of neonatal rats following hypoxic–ischemic brain damage

BackgroundPerinatal hypoxic–ischemic insult is considered a major contributor to child mortality and morbidity and leads to neurological deficits in newborn infants. There has been a lack of promising neurotherapeutic interventions for hypoxic–ischemic brain damage (HIBD) for clinical application in infants. The present study aimed to investigate the correlation between neurogenesis and basic fibroblast growth factor (bFGF) in the hippocampal dentate gyrus (DG) region in neonatal rats following HIBD. Material and methodsCell proliferation was examined by detecting BrdU signals, and the role of bFGF in cell proliferation in the DG region following neonatal HIBD was investigated. ResultsCell proliferation was induced by HIBD in the hippocampal DG of neonatal rats. Furthermore, bFGF gene expression was upregulated in the hippocampus in neonatal rats, particularly between 7 and 14 days after HIBD. Moreover, intraperitoneal injection of exogenous bFGF enhanced cell proliferation in the hippocampal DG following neonatal HIBD. ConclusionsTaken together, these data indicate that cell proliferation in the DG could be induced by neonatal HIBD, and bFGF promotes proliferation following neonatal HIBD.

Hypothesis: apo-lactoferrin-Galantamine Proteo-alkaloid Conjugate for Alzheimer's disease Intervention.

Alzheimer's disease (AD) is known to be caused by the accumulation of deformed beta amyloid and hyperphosphorylated tau proteins resulting into formation and aggregation of senile plaques and neurofibrillary tangles in the brain. Additionally, AD is associated with the accumulation of iron or metal ions in the brain which causes oxidative stress. Galantamine (Gal) is one of the therapeutic agents that has been approved for the treatment of AD, but still saddled with numerous side effects and could not address the issue of iron accumulation in the brain. The use of metal chelators to address the iron accumulation has not been successful due to toxicity and inability to address the aggregation of the plaques. We therefore hypothesize a combinatorial antioxidant–metal–chelator approach by formulating a single dosage form that has the ability to prevent the formation of free radicals, plaques and accumulation of iron in the brain. This can be achieved by conjugating Gal with apo‐lactoferrin (ApoLf), a natural compound that has high binding affinity for iron, to form an apo‐lactoferrin–galantamine proteo‐alkaloid conjugate (ApoLf–Gal) as a single dosage form for AD management. The conjugation is achieved through self‐assembly of ApoLf which results in encapsulation of Gal. ApoLf changes its conformational structure in the presence of iron; therefore, ApoLf–Gal is proposed to deliver Gal and pick up excess iron when in contact with iron. This strategy has the potential to proffer a dual neuroprotection and neurotherapeutic interventions for the management of AD.

Docosahexaenoic acid (DHA) enhances the therapeutic potential of neonatal neural stem cell transplantation post—Traumatic brain injury

Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide with 1.5 million people inflicted yearly. Several neurotherapeutic interventions have been proposed including drug administration as well as cellular therapy involving neural stem cells (NSCs). Among the proposed drugs is docosahexaenoic acid (DHA), a polyunsaturated fatty acid, exhibiting neuroprotective properties. In this study, we utilized an innovative intervention of neonatal NSCs transplantation in combination with DHA injections in order to ameliorate brain damage and promote functional recovery in an experimental model of TBI. Thus, NSCs derived from the subventricular zone of neonatal pups were cultured into neurospheres and transplanted in the cortex of an experimentally controlled cortical impact mouse model of TBI. The effect of NSC transplantation was assessed alone and/or in combination with DHA administration. Motor deficits were evaluated using pole climbing and rotarod tests. Using immunohistochemistry, the effect of transplanted NSCs and DHA treatment was used to assess astrocytic (Glial fibrillary acidic protein, GFAP) and microglial (ionized calcium binding adaptor molecule-1, IBA-1) activity. In addition, we quantified neuroblasts (doublecortin; DCX) and dopaminergic neurons (tyrosine hydroxylase; TH) expression levels. Combined NSC transplantation and DHA injections significantly attenuated TBI-induced motor function deficits (pole climbing test), promoted neurogenesis, coupled with an increase in glial reactivity at the cortical site of injury. In addition, the number of tyrosine hydroxylase positive neurons was found to increase markedly in the ventral tegmental area and substantia nigra in the combination therapy group. Immunoblotting analysis indicated that DHA+NSCs treated animals showed decreased levels of 38kDa GFAP-BDP (breakdown product) and 145kDa αII-spectrin SBDP indicative of attenuated calpain/caspase activation. These data demonstrate that prior treatment with DHA may be a desirable strategy to improve the therapeutic efficacy of NSC transplantation in TBI.

Neurotherapeutic Interventions for Psychiatric Illness.

Many patients with mental illness do not respond to common evidence-based treatments such as psychopharmacology and psychotherapy. We increasingly understand these illnesses as disorders of brain circuits, suggesting that otherwise treatment-refractory patients might be helped by direct intervention in those circuits. Non-invasive techniques for circuit intervention include electro-convulsive therapy (ECT) and transcranial magnetic stimulation (TMS). Circuits can also be targeted more directly and focally through neurosurgical intervention, including through vagus nerve stimulation (VNS), ablative neurosurgery (cingulotomy and capsulotomy), cortical brain stimulation (EpCS), or deep brain stimulation (DBS). Each of these approaches has evidence supporting its use in a major psychiatric disorder, although many have yet to demonstrate a strong clinical signal in a randomized controlled trial. New technologies that may aid in that demonstration include non-invasive techniques that can focus energy more precisely in the deep brain and invasive devices that respond in real time to changes in brain activity (closed-loop stimulation). In this article, we review the modalities and evidence base for these neurotherapeutics, with an emphasis on their clinical readiness and relative advantages.

Nutritional Treatment for Traumatic Brain Injury

Traumatic brain injury (TBI) is a significant public health concern. On average, 1.7 million persons sustain a TBI annually, and about 5.3 million Americans are living with a TBI-related disability. As the leading cause of death and disability in persons under 45 years old, there is a need for developing evidence-based interventions to reduce morbidity from this injury. So far, despite encouraging preclinical results, almost all neuroprotection trials have failed to show any significant efficacy in the treatment of patients with clinical TBI. The cascade of molecular and cellular changes after TBI involves plasticity in many different neurochemical systems, which represent putative targets for neurotherapeutic interventions. Accordingly, a successful TBI treatment may have to simultaneously attenuate many injury factors. The purpose of this review is to highlight four promising nutritional intervention options that have been identified-omega-3, zinc, vitamin D, and glutamine-and to provide an up-to-date summary regarding their apparent efficacy for affecting TBI.

Correlations between Blood–Brain Barrier Disruption and Neuroinflammation in an Experimental Model of Penetrating Ballistic-Like Brain Injury

Abstract Blood-brain barrier (BBB) disruption is a pathological hallmark of severe traumatic brain injury (TBI) and is associated with neuroinflammatory events contributing to brain edema and cell death. The goal of this study was to elucidate the profile of BBB disruption after penetrating ballistic-like brain injury (PBBI) in conjunction with changes in neuroinflammatory markers. Brain uptake of biotin-dextran amine (BDA; 3 kDa) and horseradish peroxidase (HRP; 44 kDa) was evaluated in rats at 4 h, 24 h, 48 h, 72 h, and 7 days post-PBBI and compared with the histopathologic and molecular profiles for inflammatory markers. BDA and HRP both displayed a uniphasic profile of extravasation, greatest at 24 h post-injury and which remained evident out to 48 h for HRP and 7 days for BDA. This profile was most closely associated with markers for adhesion (mRNA for intercellular adhesion molecule-1) and infiltration of peripheral granulocytes (mRNA for matrix metalloproteinase-9 [MMP-9] and myeloperoxidase staining). Improvement of BBB dysfunction coincided with increased expression of markers implicated in tissue remodeling and repair. The results of this study reveal a uniphasic and gradient opening of the BBB after PBBI and suggest MMP-9 and resident inflammatory cell activation as candidates for future neurotherapeutic intervention after PBBI.

Activation of the nuclear factor E2-related factor 2/antioxidant response element pathway is neuroprotective after spinal cord injury.

The activation of oxidative damage, neuroinflammation, and mitochondrial dysfunction has been implicated in secondary pathomechanisms following spinal cord injury (SCI). These pathophysiological processes lead to cell death and are tightly regulated by nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling. Here, we investigated whether activation of Nrf2/ARE is neuroprotective following SCI. Female Fischer rats were subjected to mild thoracic SCI (T8) using the New York University injury device. As early as 30 min after SCI, levels of Nrf2 transcription factor were increased in both nuclear and cytoplasmic fractions of neurons and astrocytes at the lesion site and remained elevated for 3 days. Treatment of injured rats with sulforaphane, an activator of Nrf2/ARE signaling, significantly increased levels of Nrf2 and glutamate-cysteine ligase (GCL), a rate-limiting enzyme for synthesis of glutathione, and decreased levels of inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) thus leading to a reduction in contusion volume and improvement in coordination. These results show that activation of the Nrf2/ARE pathway following SCI is neuroprotective and that sulforaphane is a viable compound for neurotherapeutic intervention in blocking pathomechanisms following SCI.