Chapter 10 - Polymeric nanomaterials in neuroscience

The advent of neurological disorders has taken place at an alarming rate over the past few decades. The primary challenge for the treatment and diagnosis of these neuropathies is to cross the blood–brain barrier (BBB). Nanomaterials are preferred over conventional treatments because of their nanometer range, which can interact at the molecular level with lesser adverse effects. Hence, nanomaterials can be beneficial in neuroscience because of their ability to cross BBB and compatibility for the neuronal tissues. Here, we are focusing on the neurological applications of carbon nanotubes, magnetic nanoparticles (NPs), dendrimers, nanospheres, gold NPs, liposomes, and utmost quantum dots. We have also summarized the utility and mechanism of all these NPs in the field of neuroscience, along with their prospects and approaches to avoid their substantial toxicity

Migraine and Ischemic Stroke: Deciphering the Bidirectional Pathway

Migraine and stroke are common, disabling neurological conditions with several theories being proposed to explain this bidirectional relationship. Migraine is considered as a benign neurological disorder, but research has revealed a connection between migraine and stroke, predominantly those having migraine with aura (MA). Among migraineurs, females with MA are more susceptible to ischemic stroke and may have a migrainous infarction. Migrainous infarction mostly occurs in the posterior circulation of young women. Although there are several theories about the potential relationship between MA and stroke, the precise pathological process of migrainous infarction is not clear. It is assumed that cortical spreading depression (CSD) might be one of the essential factors for migrainous infarction. Other factors that may contribute to migrainous infarction may be genetic, hormonal fluctuation, hypercoagulation, and right to left cardiac shunts. Antimigraine drugs, such as ergot alkaloids and triptans, are widely used in migraine care. Still, they have been found to cause severe vasoconstriction, which may result in the development of ischemia. It is reported that patients with stroke develop migraines during the recovery phase. Both experimental and clinical data suggest that cerebral microembolism can act as a potential trigger for MA. Further studies are warranted for the treatment of migraine, which may lead to a decline in migraine-related stroke. In this present article, we have outlined various potential pathways that link migraine and stroke

The Role of Inflammasomes in Atherosclerosis and Stroke Pathogenesis

Inflammation is a devastating outcome of cerebrovascular diseases (CVD), namely stroke and atherosclerosis. Numerous studies over the decade have shown that inflammasomes play a role in mediating inflammatory reactions post cellular injury occurring after a stroke or a rupture of an atherosclerotic plaque. In view of this, targeting these inflammatory pathways using different pharmacological therapies may improve outcomes in patients with CVD. Here, we review the mechanisms by which inflammasomes drive the pathogenesis of stroke and atherosclerosis. Also, discussed here are the possible treatment strategies available for inhibiting inflammasomes or their up-stream/down-stream mediators

Cerebro‐renal interaction and stroke

Stroke is an event causing a disturbance in cerebral function leading to death and disability worldwide. Both acute kidney injury and chronic kidney disease (CKD) are associated with an increased risk of stroke and cerebrovascular events. The underlying mechanistic approach between impaired renal function and stroke is limitedly explored and has attracted researchers to learn more for developing therapeutic intervention. Common risk factors such as hypertension, hyperphosphatemia, atrial fibrillation, arteriosclerosis, hyperhomocysteinemia, blood‐brain barrier disruption, inflammation, etc. are observed in the general population, but are high in renal failure patients. Also, risk factors like bone mineral metabolism, uremic toxins, and anemia, along with the process of dialysis in CKD patients, eventually increases the risk of stroke. Therefore, early detection of risks associated with stroke in CKD is imperative, which may decrease the mortality associated with it. This review highlights mechanisms by which kidney dysfunction can lead to cerebrovascular events and increase the risk of stroke in renal impairment. Figure representing the various steps that lead towards stroke following kidney dysfunction

Post-stroke depression: Chaos to exposition

•Post Stroke Depression (PSD) is a major neuropsychological outcome of stroke.•Symptoms materialize within months of stroke, progressing to a long-term ailment.•Identification of PSD biomarkers can help revolutionize treatment for PSD. Cerebral ischemia contributes to significant disabilities worldwide, impairing cognitive function and motor coordination in affected individuals. Stroke has severe neuropsychological outcomes, the major one being a stroke. Stroke survivors begin to show symptoms of depression within a few months of the incidence that overtime progresses to become a long-term ailment. As the pathophysiology for the progression of the disease is multifactorial and complex, it limits the understanding of the disease mechanism completely. Meta-analyses and randomized clinical trials have shown that intervening early with tricyclic antidepressants and selective serotonin receptor inhibitors can be effective. However, these pharmacotherapies possess several limitations that have given rise to newer approaches such as brain stimulation, psychotherapy and rehabilitation therapy, which in today's time are gaining attention for their beneficial results in post-stroke depression (PSD). The present review highlights numerous factors like lesion location, inflammatory mediators and genetic abnormalities that play a crucial role in the development of depression in stroke patients. Further, we have also discussed various mechanisms involved in post-stroke depression (PSD) and strategies for early detection and diagnosis using biomarkers that may revolutionize treatment for the affected population. Towards the end, along with the preclinical scenario, we have also discussed the various treatment approaches like pharmacotherapy, traditional medicines, psychotherapy, electrical stimulation and microRNAs being utilized for effectively managing PSD

Neuroimmune crosstalk and evolving pharmacotherapies in neurodegenerative diseases

Neurodegeneration is characterized by gradual onset and limited availability of specific biomarkers. Apart from various aetiologies such as infection, trauma, genetic mutation, the interaction between the immune system and CNS is widely associated with neuronal damage in neurodegenerative diseases. The immune system plays a distinct role in disease progression and cellular homeostasis. It induces cellular and humoral responses, and enables tissue repair, cellular healing and clearance of cellular detritus. Aberrant and chronic activation of the immune system can damage healthy neurons. The pro‐inflammatory mediators secreted by chief innate immune components, the complement system, microglia and inflammasome can augment cytotoxicity. Furthermore, these inflammatory mediators accelerate microglial activation resulting in progressive neuronal loss. Various animal studies have been carried out to unravel the complex pathology and ascertain biomarkers for these harmful diseases, but have had limited success. The present review will provide a thorough understanding of microglial activation, complement system and inflammasome generation, which lead the healthy brain towards neurodegeneration. In addition to this, possible targets of immune components to confer a strategic treatment regime for the alleviation of neuronal damage are also summarized

Multicenter International Society for Immunotherapy of Cancer Study of the Consensus Immunoscore for the Prediction of Survival and Response to Chemotherapy in Stage III Colon Cancer.

PURPOSE The purpose of this study was to evaluate the prognostic value of Immunoscore in patients with stage III colon cancer (CC) and to analyze its association with the effect of chemotherapy on time to recurrence (TTR). METHODS An international study led by the Society for Immunotherapy of Cancer evaluated the predefined consensus Immunoscore in 763 patients with American Joint Committee on Cancer/Union for International Cancer Control TNM stage III CC from cohort 1 (Canada/United States) and cohort 2 (Europe/Asia). CD3+ and cytotoxic CD8+ T lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The primary end point was TTR. Secondary end points were overall survival (OS), disease-free survival (DFS), prognosis in microsatellite stable (MSS) status, and predictive value of efficacy of chemotherapy. RESULTS Patients with a high Immunoscore presented with the lowest risk of recurrence, in both cohorts. Recurrence-free rates at 3 years were 56.9% (95% CI, 50.3% to 64.4%), 65.9% (95% CI, 60.8% to 71.4%), and 76.4% (95% CI, 69.3% to 84.3%) in patients with low, intermediate, and high immunoscores, respectively (hazard ratio [HR; high v low], 0.48; 95% CI, 0.32 to 0.71; P = .0003). Patients with high Immunoscore showed significant association with prolonged TTR, OS, and DFS (all P .12). CONCLUSION This study shows that a high Immunoscore significantly associated with prolonged survival in stage III CC. Our findings suggest that patients with a high Immunoscore will benefit the most from chemotherapy in terms of recurrence risk