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Amyotrophic lateral sclerosis (ALS) is a debilitating disease with poor prognosis. The pathophysiology of ALS is commonly debated, with theories involving inflammation, glutamate excitotoxity, oxidative stress, mitochondria malfunction, neurofilament accumulation, inadequate nutrients or growth factors, and changes in glial support predominating. These underlying pathological mechanisms, however, act together to weaken the blood brain barrier and blood spinal cord barrier, collectively considered as the blood central nervous system barrier (BCNSB). Altering the impermeability of the BCNSB impairs the neurovascular unit, or interdependent relationship between the brain and advances the concept that ALS is has a significant neurovascular component contributing to its degenerative presentation. This unique categorization of ALS opens a variety of treatment options targeting the reestablishment of BCNSB integrity. This review will critically assess the evidence implicating the significant neurovascular components of ALS pathophysiology, while also offering an in-depth discussion regarding the use of stem cells to repair these pathological changes within the neurovascular unit.

Stroke pathology and its treatments conventionally focus on the brain. Probing inflammation, a critical secondary cell death mechanism in stroke, has been largely relegated to the brain. To this end, peripheral inflammation has emerged as an equally potent contributor to the onset and progression of stroke secondary cell death. Here, we review novel concepts on peripheral organs displaying robust inflammatory response to stroke. These inflammation-plagued organs include the spleen, cervical lymph nodes, thymus, bone marrow, gastrointestinal system, and adrenal glands, likely converging their inflammatory effects through B and T-cells. Recognizing the significant impact of this systemic inflammation, we also discuss innovative stroke therapeutics directed at sequestration of peripheral inflammation. This review paper challenges the paradigm of a brain-centered disease pathology and treatment and offers a peripheral approach to our stroke understanding.

Stem cell transplantation is historically understood as a powerful preclinical therapeutic following stroke models. Current clinical strategies including clot busting/retrieval are limited by their time windows (tissue plasminogen activator: 3–4 h) and inevitable reperfusion injuries. However, 24+ h post-stroke, stem cells reduce infarction size, improve neurobehavioral performance, and reduce inflammatory agents including interleukins. Typically, interleukin-6 (IL-6) is regarded as proinflammatory, and thus, preclinical studies often discuss it as beneficial for neurological recuperation when stem cells reduce IL-6′s expression. However, some studies have also demonstrated neurological benefit with upregulation of IL-6 or preconditioning of stem cells with IL-6. This review specifically focuses on stem cells and IL-6, and their occasionally disparate, occasionally synergistic roles in the setting of ischemic cerebrovascular insults.

Interleukin (IL)-6 is a unique cytokine due to its dual signaling, with one pathway being pro-inflammatory (trans) and the other homeostatic (classical). Both of these pathways have been implicated in neuroinflammation following stroke, with initial inflammatory mechanisms being protective and later anti-inflammatory signaling promoting ischemic tissue recovery. IL-6 plays a major role in stroke pathology. However, given these distinctive IL-6 signaling consequences, IL-6 is a difficult cytokine to target for stroke therapies. Recent research suggests that the ratio between the pro-inflammatory binary IL6:sIL6R complex and the inactive ternary IL6:sIL6R:sgp130 complex may be a novel way to measure IL-6 signaling at different time points following ischemic injury. This ratio may approximate functional consequences on individualized stroke therapies, allowing clinicians to determine whether IL-6 agonists or antagonists should be used at specific time points.

This review focuses on the recent literature regarding the role of the gut-brain axis (GBA) following ischemic stroke.Stroke is the 5th leading cause of death and disability in the United States; however, few therapies have been developed to improve prognoses. There is a plethora of evidence suggesting peripheral inflammatory responses play a large role in the pathogenesis of stroke. Additionally, hyperglycemic conditions may play a significant role in worsening stroke outcomes due to microbiome dysbiosis.Recent research has illuminated the vital role of the GBA in propagating poor clinical outcomes, such as hemorrhagic transformation, following ischemic stroke. Considering this detrimental consequence of stroke, and the apparent role of the GBA role, future therapeutics should aim to mitigate this peripheral contribution to stroke complications.

In a recent Nature Medicine publication, Sailor et al.

Intracranial aneurysm (IA) rupture is a common cause of subarachnoid hemorrhage (SAH) with high mortality and morbidity. Inflammatory interleukins (IL), such as IL-6, play an important role in the occurrence and rupture of IA causing SAH. With this review we aim to elucidate the specific role of IL-6 in aneurysm formation and rupture in preclinical and clinical studies. IL-6 is a novel cytokine in that it has pro-inflammatory and anti-inflammatory signaling pathways. In preclinical and clinical studies of IA formation, elevated and reduced levels of IL-6 are reported. Poor post-rupture prognosis and increased rupture risk, however, are associated with higher levels of IL-6. By better understanding the relationships between IL-6 and IA formation and rupture, IL-6 may serve as a biomarker in high-risk populations. Furthermore, by better understanding the IL-6 signaling mechanisms in IA formation and rupture, IL-6 may optimize surveillance and treatment strategies. This review examines the association between IL-6 and IA, while also suggesting future research directions.

This literature review focuses on the role of IL-6 in TBI or PTSD-induced neuroinflammation. While TBI and PTSD are widely prevalent, these diagnoses are particularly common amongst veterans. Given the role of IL-6 in neuroprotection acutely, compared to detrimental chronically, targeting this cytokine at specific time points may be beneficial in modulating neuroinflammation. Current treatments for TBI or PTSD are variably affective. By reviewing the role of IL-6 in these two diagnoses, future studies can focus on therapeutics to treat neuroinflammation and ultimately reduce the devastating impacts of neuroinflammation on cognition in PTSD and TBI.

This literature review focuses on the underlying pathophysiology of TBI and PTSD symptoms, while also examining the plethora of stem cell treatment options to ameliorate these neuronal and functional changes. As more veterans return suffering from TBI and/or PTSD, it is vital that researchers discover novel therapies to mitigate the detrimental symptoms of both diagnoses. A variety of stem cell treatments have been studied and offer hopeful options for TBI and PTSD recovery.

Thoracolumbar lateral interbody fusions (tLLIF) are one tool in the spine surgeon's toolbox to indirectly decompress neuroforamina while also improving segmental lordosis in a biomechanically distinct manner from posterior fusions. When part of a concomitant posterior construct, hardware failure (HF), sometimes requiring revision surgery, can occur. We sought to study the relationship between tLLIF and HF.We conducted a retrospective study on consecutive patents who underwent tLLIF at a single academic center between January 2012 and December 2021 by seven unique neurosurgeons. Patients were excluded if they had no posterior instrumentation within their construct or if they had less than six months of follow-up. Hardware failure was defined as screw breakage or rod fracture seen on postoperative imaging.232 patients were identified; 6 (2.6 %) developed HF throughout a mean follow-up of 1182 days (range =748-1647 days). Adjacent segment disease was the most common pathology addressed (75 patients (32.3 %)). The amount of posterior instrumentation both in the surgery in question and in the total construct were significantly higher in the HF cohort (4.33 ± 1.52 levels, 5.83 ± 3.36 levels) versus the non-HF cohort (2.08 ± 0.296 levels, p = 0.014; 2.86 ± 0.316 levels, p = 0.003, respectively). The number of interbody devices added in the index surgery and in the entire construct were both significantly higher in the HF cohort (3.33 ± 0.666 interbody devices, 3.33 ± 0.666 devices) than in the non-HF cohort (1.88 ± 0.152 interbody devices, p = 0.002; 2.31 ± 0.158 devices, p = 0.036, respectively). Higher amounts of lateral levels of fusion approached significance for association with HF (HF: 2.67 ± 0.844 levels, no HF: 1.73 ± 1.26 levels, p = 0.076). On multivariate analysis, only the number of interbody devices added in the index surgery was predictive of HF (Odds ratio=2.3, 95 % confidence interval=1.25-4.23, p = 0.007).Greater levels of posterior fusion, and greater numbers of interbody devices in an index surgery and in a construct as a whole, were associated with higher rates of HF in our cohort of patients with tLLIF. Greater numbers of lateral segments fused in this population may also be related to HF.

Epigenetic changes in stroke may revolutionize cell-based therapies aimed at reducing ischemic stroke risk and damage. Epigenetic changes are a novel therapeutic target due to their specificity and potential for reversal. Possible targets for epigenetic modification include DNA methylation and demethylation, post-translational histone modification, and the actions of non-coding RNAs such as microRNAs. Many of these epigenetic modifications have been reported to modulate atherosclerosis development and progression, ultimately contributing to stroke pathogenesis. Furthermore, epigenetics may play a major role in inflammatory responses following stroke. Stem cells for stroke have demonstrated safety in clinical trials for stroke and show therapeutic benefit in pre-clinical studies. The efficacy of these cell-based interventions may be amplified with adjunctive epigenetic modifications. This review advances the role of epigenetics in atherosclerosis and inflammation in the context of stroke, followed by a discussion on current stem cell studies modulating epigenetics to ameliorate stroke damage.

Parkinson’s disease is the second most common neurodegenerative disease. Insidious and progressive, this disorder is secondary to the gradual loss of dopaminergic signaling and worsening neuroinflammation, affecting patients’ motor capabilities. Gold standard treatment includes exogenous dopamine therapy in the form of levodopa–carbidopa, or surgical intervention with a deep brain stimulator to the subcortical basal ganglia. Unfortunately, these therapies may ironically exacerbate the already pro-inflammatory environment. An alternative approach may involve cell-based therapies. Cell-based therapies, whether endogenous or exogenous, often have anti-inflammatory properties. Alternative strategies, such as exercise and diet modifications, also appear to play a significant role in facilitating endogenous and exogenous stem cells to induce an anti-inflammatory response, and thus are of unique interest to neuroinflammatory conditions including Parkinson’s disease. Treating patients with current gold standard therapeutics and adding adjuvant stem cell therapy, alongside the aforementioned lifestyle modifications, may ideally sequester inflammation and thus halt neurodegeneration.

BackgroundThe repercussions of climate change threaten the population with an increased prevalence of extreme climate events. We explored the impact of climate change induced sea level rise (SLR) and tropical cyclone (TC) exposure on mental illness symptom prevalence.MethodsUsing three datasets, TC exposure scores were calculated for each subject to determine how exposure affects posttraumatic stress disorder (PTSD), anxiety, and major depressive disorder (MDD) symptom prevalence. Inundation mapping of various SLR and storm surge (SS) scenarios were performed for the susceptible region of Miami-Dade and Broward counties to determine the population impact of flooding.ResultsWe found an elevated risk of mental illness symptoms from exposure to more high-intensity TCs and identified demographic variables that may contribute to this risk. Furthermore, inundation mapping demonstrated severe and widespread impact of SLR and SS on the mental health of communities.LimitationsThis study did not include data directly measuring comorbidity, resilience, preparedness, or ability to adapt to climate change. Also, multiple imputation using chained equations may have been imperfect. Finally, when conducting inundation mapping, static mapping may overestimate flooding severity.ConclusionThe impacts of climate change have been frequently studied in terms of physical health, natural disaster prevalence, and economic impacts, but rarely on mental health burden. However, it is vital that national, state, and local governments develop and deploy plans to address mental health needs along with expenditures for protecting infrastructure, the economy, and physical health from the combined effects of SLR and climate change-induced natural disasters.

The repercussions of climate change threaten the population with an increased prevalence of extreme climate events. We explored the impact of climate change induced sea level rise (SLR) and tropical cyclone (TC) exposure on mental illness symptom prevalence.Using three datasets, TC exposure scores were calculated for each subject to determine how exposure affects posttraumatic stress disorder (PTSD), anxiety, and major depressive disorder (MDD) symptom prevalence. Inundation mapping of various SLR and storm surge (SS) scenarios were performed for the susceptible region of Miami-Dade and Broward counties to determine the population impact of flooding.We found an elevated risk of mental illness symptoms from exposure to more high- intensity TCs and identified demographic variables that may contribute to this risk. Furthermore, inundation mapping demonstrated severe and widespread impact of SLR and SS on the mental health of communities.This study did not include data directly measuring comorbidity, resilience, preparedness, or ability to adapt to climate change. Also, multiple imputation using chained equations may have been imperfect. Furthermore, there is uncertainty in predicting and mapping SLR and TC intensity, which limits complete confidence in our SS predictions.The impacts of climate change have been frequently studied in terms of physical health, natural disaster prevalence, and economic impacts, but rarely on mental health burden. However, it is vital that national, state, and local governments develop and deploy plans to address mental health needs along with expenditures for protecting infrastructure, the economy, and physical health from the combined effects of SLR and climate change-induced natural disasters.

Subarachnoid hemorrhage has a poor prognosis due to the wide array of associated complications such as vasospasm, early brain injury, cortical spreading depression, oxidative stress, inflammation, and apoptosis. Each of these complications increases the risk of delayed cerebral ischemia (DCI), but recent research has suggested microclots play a substantial role in DCI incidence. This review will focus on the underlying inflammatory and coagulative mechanisms of microthrombosis while also outlining the current literature relating microclot burden to DCI. With a better understanding DCI pathophysiology as it relates to microthrombosis, more effective therapies can be developed in the future to improve clinical outcomes of SAH.