Exosome therapies improve outcome in rodents with ischemic stroke; meta-analysis.

OBJECTIVE: Exosome therapy has been theorized to be safer, more effective, and less cumbersome in replacing stem cell therapies for tissue repair and regeneration. There remains considerable uncertainty on whether exosome therapy is efficacious and safe for recovery from brain injury due to cerebral infarction. There is growing consensus that systematic reviews of data, from preclinical studies which yielded conflicting and confusing results, can provide valuable directions for novel therapeutic options for several clinical conditions. This study systematically evaluated the efficacy of exosome therapy in ischemic stroke in preclinical studies in rodent models. METHODS: We reviewed existing literature on exosome therapy in rodent stroke models from various databases, and reviewed the interventional measures, and outcome measures systematically, with changes in the infarct volume and functional scores as outcome parameters. Seventeen homogeneous studies were found qualitatively acceptable for meta-analysis. The study used software RevMan 5.3 to conduct the meta-analysis (PROSPERO Register Number: CRD42022314138) RESULTS: Compared to placebo, exosomes treated ischemic stroke models showed significantly reduced brain infarct volume and improved functional recovery on days 7 and 28. Though there are no safety concerns reported in any preclinical studies, there is insufficient data to make robust conclusions on the therapy's safety. INTERPRETATION: Therapy with subcellular exosomes is a promising treatment to be explored further in animal ischemic stroke models to arrive at robust conclusions for its safety and therapeutic dosage. This must precede Phase I and II- human randomized clinical trials to establish the safety and proof of concept of efficacy of exosome therapy in human ischemic stroke.

A cross-sectional study of COVID-19 outbreak in Indian population.

Background: Presently India is the second most populous country in the world with an estimated population of 1.4 billion people and has recently been affected by COVID-19 pandemic and subsequent mutant viral outbreak. To date, India has administered its population with over 1.30 billion cumulative doses of COVID-19 vaccine. The consequences of COVID-19 vaccination on the outbreak in India has not been reported until now. Therefore, we probed to assess the impact of COVID-19 outbreak in India from December 2019 to December 2021. Methods: Indian COVID-19 related data were extracted from "ourworldindata.org" and "cowin.gov.in" databases. The incidence rate of COVID-19 per million people was calculated and other parameters such as new cases, positive rate, reproduction rate, new death and stringency index values were extracted from the database for statistical analysis. Results: Data indicate that the COVID-19 positive rate declined as the number of vaccinations rose over time. The Pearson correlation values between new cases and the cumulative percentage of vaccination or the percentage of fully vaccinated population showed no correlation (P < 0.01). COVID-19 vaccination has significantly decreased the R-value and positive rate of SARS-CoV-2 in India (P < 0.01). Furthermore, containment measures showed no correlation with the incidence rate of SARS-CoV-2 in India which may be in contradictory to the global trends. Conclusion: Vaccination against COVID-19 was efficacious in the control of the SARS-CoV-2 outbreak and the decrease in the positive rate. Further, the containment measures had no effect on the spread of COVID-19 infection in India, thus far.

Short-term Effect of Noninvasive Brain Stimulation Techniques on Motor Impairment in Chronic Ischemic Stroke: A Systematic Review with Meta-Analysis.

Background: In recent years, noninvasive brain stimulation (NIBS) has shown promise for stroke rehabilitation as a novel nonpharmaceutical neuromodulatory intervention with attractive neurophysiological theories backing it up. Objective: To find out the short-term effects of NIBS techniques on motor impairment in chronic ischemic stroke. Materials and Methods: A systematic review with meta-analysis was performed separately for transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), and studies that combined both, utilizing various databases for a period spanning from 2001 to 2019. Good-quality randomized controlled trials (RCTs) on chronic ischemic stroke cases with homogeneous clinical upper motor short-term outcome measures were considered for the meta-analysis. RevMan 5.1 software was used for the meta-analysis. Meta-analysis registration: CRD42021196299; https://www.crd.york.ac.uk/PROSPERO. Results: A total of 319 studies were identified initially. After necessary filters to comply with the strict recruitment criteria, only four studies qualified, two each for tDCS and TMS and none qualified for analysis under the combined category. tDCS showed a nonsignificant effect on the upper limb motor function improvement (-0.10 [95% confidence interval {CI}: -0.84 to 0.64; I2 0%; P = 0.8]), whereas the repetitive TMS showed a significant effect (0.75 [95% CI: 0.03-1.48; I2 0%; P = 0.04]). The safety analysis did not reveal any major concerns for several published protocols. Conclusions: tDCS alone did not significantly benefit motor recovery; rTMS was effective in providing immediate functional benefits in chronic ischemic stroke. While the current stroke rehabilitation protocols with NIBS appear safe, more good-quality stratified RCTs with more innovative experimental protocols are needed to analyze and quantify the efficacy of these techniques in stroke rehabilitation.

Recent preclinical study offers a promising clue: Role of regulatory T cells as biomarkers in migraine.

The exact etiology of migraine has not yet been fully understood. There is no specific diagnostic test for migraine and is often misdiagnosed like all other types of headaches. The lack of a diagnostic test is also a significant impediment to migraine management. In previous clinical studies, the author and his team found decreased levels of CD4+CD25+ Regulatory T cells (Treg) in migraine patients. These reductions were significant in the ictal phase of migraine, regardless of the subtype of migraines. Interestingly, the recent preclinical study demonstrated a significant improvement in nitroglycerine induced headache by activating Treg cells. Therefore, the author argued that peripheral Treg cell levels can be a therapeutically relevant biomarker for migraine.

Preclinical animal studies in ischemic stroke: Challenges and some solutions.

Despite the impressive efficacies demonstrated in preclinical research, hundreds of potentially neuroprotective drugs have failed to provide effective neuroprotection for ischemic stroke in human clinical trials. Lack of a powerful animal model for human ischemic stroke could be a major reason for the failure to develop successful neuroprotective drugs for ischemic stroke. This review recapitulates the available cerebral ischemia animal models, provides an anatomical comparison of the circle of Willis of each species, and describes the functional assessment tests used in these ischemic stroke models. The distinct differences between human ischemic stroke and experimental stroke in available animal models is explored. Innovative animal models more closely resembling human strokes, better techniques in functional outcome assessment and better experimental designs generating clearer and stronger evidence may help realise the development of truly neuroprotective drugs that will benefit human ischemic stroke patients. This may involve use of newer molecules or revisiting earlier studies with new experimental designs. Translation of any resultant successes may then be tested in human clinical trials with greater confidence and optimism.

Outcome of human peripheral nerve repair interventions using conduits: a systematic review.

BACKGROUND & OBJECTIVE: Peripheral nerve injury is very common, but repair is a challenging medical problem. Advances in medical sciences and technologies have however made tremendous breakthroughs in understanding repair mechanisms in nerve injury making this a fascinating area in neurotherapeutics. However, a systematic analysis of existing data is lacking, the present study was attempted to review existing literature in nerve repair studies in human beings and analyse outcome systematically. METHODS: A detailed search was made from various databases published in the last 10 years. The studies were included based on availability of data on the age of the patients, type of injuries, type of intervention and also on the minimal follow up period. Studies satisfying these criteria were subjected to a homogeneity test. On 263 patients from 3 homogeneous studies outcome parameters such as the functional improvement, sensory and motor recovery parameters were analysed. RESULTS: Results showed that conduits were safe and significantly more effective compared to the conventional sutures in effecting repair of sensory nerve injuries (Odds ratio 3.78; P < .00001). CONCLUSION: In conclusion, repair of human sensory peripheral nerve using conduits is safe and more effective than direct nerve suture.

Reduction of CD4(+)CD25(+) regulatory T-cells in migraine: Is migraine an autoimmune disorder?

Migraine is believed to be a chronic neurological disorder with the exact aetiology being unknown. But, there is a debate on the role of immune dysfunction in migraine pathophysiology. Hence, authors made a debut attempt to explore the link between lymphocyte subset populations and migraine. A significant increase in CD4(+) and decrease in CD8(+) population were observed in migraine patients compared to healthy volunteers. Interestingly, the immunoregulator CD4(+)CD25(+) levels were less in migraine patients compared to the healthy volunteers. The results of the present study indicate that failure of immunoregulation could be implicated in the pathophysiology of migraine.

Increased incidence of migraine in women correlates with obstetrics and gynaecological surgical procedures.

Migraine is a common chronic neurological disorder; yet no possible aetiology has been identified so far. There is a debate that migraine worsens in women who undergo procedures such as hysterectomy, dilation and curettage (D&C) or cesarean section for delivery. Hence, the present study was attempted to explore the link between procedures like D&C, hysterectomy and cesarean section for delivery and the prevalence of migraine in women. A total of 185 migraine patients were screened based on the inclusion and exclusion criteria of the International Headache Classification guidelines and 70 females who satisfied the inclusion criteria were included for the study. Of the 70 female patients, the numbers of married and unmarried women were 47 and 27, respectively. About 36 married women (80%, 95% CI: 0.146-0.104) had undergone the procedures related to obstetrics and gynaecology as per their medical history. Interestingly, 12 patients (33%, 95% CI: 0.148-0.176) had not experienced migraine attack prior to the above mentioned surgeries. Although, the age adjusted incidence of diagnosed migraine per 100,000 populations showed higher risk between 16-20 years of age (95% CI: 0.104-0.121), significant risk (95% CI: 0.086-0.113) was also observed in the women of 31-35 years age group in the present study. Based on the present study, surgeries such as D&C, hysterectomy and cesarean section for delivery increased the prevalence of migraine in women. Therefore, such procedures should be avoided unless otherwise essential, particularly in patients with positive past history of migraine.