CNS & neurological disorders drug targets最新文献

Background: A limited subgroup of multiple sclerosis (MS) patients present with a longterm disease evolution characterized by a limited disease progression, known as benign MS (BMS). Chitinase 3-like-1 (CHI3L1) levels are sensitive to inflammatory processes and may play a role in the pathogenesis of MS. In this observational, cross-sectional study, we aimed to evaluate the implications of serum CHI3L1 and inflammatory cytokines in BMS patients treated with interferon β-1b for over a decade.

Methods: We collected serum samples from 17 BMS patients and 17 healthy controls (HC) to measure serum CHI3L1 levels and a Th17 panel of inflammatory cytokines. Serum levels of CHI3L1 were analysed using the sandwich ELISA method and the Th17 panel was assessed using the multiplex XMap technology on a Flexmap 3D Analyzer.

Results: Serum CHI3L1 levels did not differ significantly from HC. We identified a positive correlation between CHI3L1 levels and relapses during treatment.

Conclusion: Our findings suggest that there are no differences in serum CHI3L1 levels between BMS patients and HC. However, serum CHI3L1 levels are sensitive to clinical inflammatory activity and may be associated with relapses in BMS patients.

Parkinson's disease is the second most common neurodegenerative disease affecting millions of people worldwide. Despite the crucial threat it poses, currently, no specific therapy exists that can completely reverse or halt the progression of the disease. Parkinson's disease pathology is driven by neurodegeneration caused by the intraneuronal accumulation of alpha-synuclein (α-syn) aggregates in Lewy bodies in the substantia nigra region of the brain. Parkinson's disease is a multiorgan disease affecting the central nervous system (CNS) as well as the autonomic nervous system. A bidirectional route of spreading α-syn from the gut to CNS through the vagus nerve and vice versa has also been reported. Despite our understanding of the molecular and pathophysiological aspects of Parkinson's disease, many questions remain unanswered regarding the selective vulnerability of neuronal populations, the neuromodulatory role of the locus coeruleus, and alpha-synuclein aggregation. This review article aims to describe the probable factors that contribute to selective neuronal vulnerability in Parkinson's disease, such as genetic predisposition, bioenergetics, and the physiology of neurons, as well as the interplay of environmental and exogenous modulators. This review also highlights various therapeutic strategies with cell transplants, through viral gene delivery, by targeting α-synuclein and aquaporin protein or epidermal growth factor receptors for the treatment of Parkinson's disease. The application of regenerative medicine and patient-specific personalized approaches have also been explored as promising strategies in the treatment of Parkinson's disease.

Neurologic injury continues to be a debilitating worldwide disease with high morbidity and mortality. The systemic sequelae of a neural insult often lead to prolonged hospital stays and challenging nutritional demands that contribute to poorer prognoses. Clinical management of a given condition should prioritize preserving the homeostatic parameters disrupted by inflammatory response cascades following the primary insult. This focused review examines the reciprocal relationship between electrolyte disturbance and neurologic injury. A prolonged electrolyte imbalance can significantly impact morbidity and mortality in neurologic injuries. A detailed overview of the major electrolytes and their physiologic, iatrogenic, and therapeutic implications are included. The pathophysiology of how dysnatremias, dyskalemias, dyscalcemias, and dysmagnesemias occur and the symptoms they can induce are described. The manifestations in relation to traumatic brain injury, status epilepticus, and acute ischemic stroke are addressed. Each type of injury and the strength of its association with a disruption in either sodium, potassium, calcium, or magnesium is examined. The value of supplementation and replacement is highlighted with an emphasis on the importance of early recognition in this patient population. This review also looks at the current challenges associated with correcting imbalances in the setting of different injuries, including the relevant indications and precautions for some of the available therapeutic interventions. Based on the findings of this review, there may be a need for more distinct clinical guidelines on managing different electrolyte imbalances depending on the specified neurologic injury. Additional research and statistical data on individual associations between insult and imbalance are needed to support this potential future call for context-based protocols.

Objective: To evaluate the safety and effectiveness of levetiracetam and phenytoin by evaluating the events of seizure termination and recurrence in children.

Methods: We used the internet databases PubMed, Embase, and Google Scholar to conduct a literature search for the appropriate studies. A meta-analysis was performed to calculate the odds ratio using fixed and random-effects models.

Results: We identified 15 studies that were eligible for the meta-analysis. The incidence of seizure termination within 24 h was 76.9% for levetiracetam and 70.5% for phenytoin. Levetiracetam had a higher number of seizure termination events than phenytoin (P = 0.005, I² = 66%). The incidence of seizure recurrence within 24 h was 10% for levetiracetam and 15.6% for phenytoin. Phenytoin had a significantly higher number of seizure recurrence events than levetiracetam (P = 0.00007, I² = 21%).

Conclusion: The efficacy and safety of levetiracetam are superior to that of phenytoin in children with status epilepticus. Large Randomized Controlled Trial studies are needed to confirm the result in children.