Neuroaids

HIV-associated sensory neuropathies (HIV-SN) are prevalent in >50% of patients aged over 45 years many of which report moderate to severe chronic pain. Previous preclinical studies have investigated the mechanisms by which HIV-1 causes sensory neuropathies and pain-like behaviors. The aim of the present study is to delineate the role of chronic HIV-1 trans-activator of transcription protein (Tat) exposure in the development of neuropathy in mice. The temporal effects of conditional Tat expression on the development of hypersensitivity to mechanical (von Frey filaments) and thermal (heat or cold) stimuli were tested in male and female mice that transgenically expressed HIV-1 Tat in a doxycycline-inducible manner...

In the United States, the Centers for Disease Control and Prevention (CDC) terms HIV and tobacco use among the ten most important public health challenges we face today. In the last decade, there has been a remarkable decrease in the number of deaths due to HIV/AIDS, especially after the widespread availability and use of combination antiretroviral therapy (cART). However, people living with HIV/AIDS have a heightened risk of chronic complications and comorbidities, including neurological disorders. Around 40-60 % of HIV-infected individuals progress to NeuroAIDS, a group of disorders caused primarily by HIV-mediated damage to the central and peripheral nervous systems, despite receiving cART...

INTRODUCTION: Motor skills are the domains most often affected by stroke, but a comprehensive assessment of motor function is often impractical in the acute setting. It could be useful to have a brief simple tool allowing the stratification of patients at the time of inclusion in clinical studies. Hence, our primary objective was to evaluate whether the baseline NIH Stroke Scale limb motor score (b-NIHSS-LMS), obtained by summing the four motor items 5a to 6b of the NIHSS, is associated with functional recovery assessed by the modified Rankin Score (mRS)...

Intranasal drug delivery is one of the uprising areas of the research in targeting drug to the brain. Nose to brain drug delivery follows the olfactory pathway and purportedly known to be more efficient to deliver neuro-therapeutics to the brain by circumventing the BBB and thereby increasing bioavailability of drugs in the brain. The advantage of this method is non-invasiveness, rapid onset of action and helps to achieve site specific delivery. In this research work nanosuspension were prepared using combination of antiretroviral agents for Neuro-AIDS treatment...

INTRODUCTION: HIV infection causes a wide range of neurological complications, many of which are among the most common complications of chronic HIV infection in the era of combined antiretroviral therapy. These neurological conditions arise due to complex interactions between HIV viral proteins and neuronal and glial cells that lead to the activation of various inflammatory and neurotoxic pathways across the nervous system. AREAS COVERED: This review summarizes the current literature on the pathogenesis and clinical manifestations of neurological injuries associated with HIV in the brain, spinal cord, and peripheral nervous system...

The clinical efficacy of antiretroviral therapy in NeuroAIDS is primarily limited by the low perfusion of the drug to the brain. The objective of the current investigation was to design and develop an in situ mucoadhesive gel loaded with darunavir to assess the feasibility of brain targeting through the intranasal route. Preliminary batches (F1-F9) were prepared and evaluated for various pharmaceutical characteristics. A full factorial design of the experiment was applied to optimize and assess the effect of two influencing variables (Carbopol 934P (X1 ) and Poloxamer 407 (X2 )) on the response effects (gelation temperature (Y1 ) and % drug release (Y2 ) at 8 h)...

PURPOSE OF REVIEW: HIV-associated neurocognitive disorders (HAND) continues to be prevalent in people living with HIV despite antiretroviral therapy. However, understanding disease mechanisms and identifying therapeutic avenues has been challenging. One of the challenges is that HAND is a heterogeneous disease and that patients identified with similar impairments phenotypically may have very different underlying disease processes. As the NeuroAIDS field is re-evaluating the approaches used to identify patients with HIV-associated neurological impairments, we propose the subtyping of patients into biotypes based on viral and immune pathogenesis...

OBJECTIVE: MLC601/MLC901 has demonstrated neuroprotective and neuroregenerative properties that enhance neurological recovery in stroke and traumatic brain injury. We aimed to evaluate its safety and potential efficacy in patients with severe spinal cord injury. METHODS: Patients with American Spinal Injury Association (ASIA) Impairment Scale (AIS) A and B were included in an open-label cohort study. Each received a course of MLC601/MLC901 for 6 months in addition to standard care and rehabilitation...

INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of death in young adults globally and 90% of cases are mild TBI. Treatment to facilitate recovery after TBI is needed. Traditional medicine MLC901 (NeuroAiD II) with neuroprotective and neuroproliferative properties in cellular and animal models of brain injury showed TBI-associated cognitive improvement in mild or moderate TBI. METHODS AND ANALYSIS: This is a randomised placebo-controlled trial, with 6-month treatment and 9-month follow-up, to determine the safety and efficacy of MLC901 in improving cognitive function in patients with cognitive impairment following mild TBI...

Astrocyte reactivity, a phenomenon observed in a variety of neurodegenerative disorders, can have both beneficial and detrimental manifestations which significantly affect neuronal physiology. In neuroAIDS, reactive astrocytes have been observed to severely affect the neuronal population present in their vicinity. Calcium signaling plays a central role in mediating astrocyte reactivity. Coronin 1A, an actin-binding protein, majorly reported in hematopoietic cells, regulates cell activity in a calcium-dependent manner, but its role in astrocyte physiology and reactivity is largely unknown...

OBJECTIVES: Preclinical and clinical studies indicate a role for MLC901 (NeuroAiD II) in Alzheimer's disease (AD). The primary aim was to investigate its safety as add-on therapy to standard treatment and the secondary aims its effect on cognition and slowing disease progression. DESIGN: Randomized double-blind placebo-controlled delayed-start study. SETTING AND PARTICIPANT: Patients with mild to moderate probable AD by NINCDS-ADRDA criteria, stable on acetylcholinesterase inhibitors or memantine (n = 125), were randomized to receive MLC901 (early starters) or placebo (delayed starters) for 6 months, followed by a further 6 months when all patients received MLC901, in a delayed-start design (clinical trial registration: ClinicalTrials...

As our understanding of changes to the neurological system has improved, it has become clear that patients who have contracted human immunodeficiency virus type 1 (HIV-1) can potentially suffer from a cascade of neurological issues, including neuropathy, dementia, and declining cognitive function. The progression from mild to severe symptoms tends to affect motor function, followed by cognitive changes. Central nervous system deficits that are observed as the disease progresses have been reported as most severe in later-stage HIV infection...

BACKGROUND: People with HIV (PWH) have increased frailty risk at younger ages compared with the general population. Multimorbidity is associated with frailty, yet effects of specific comorbidities on transition to frailty in PWH are unknown. SETTING: Prospective study of 219 PWH age 45 years or older in the National NeuroAIDS Tissue Consortium. METHODS: Frailty status was categorized using Fried frailty phenotype criteria. Comorbidities [bone disease, cardiovascular disease, cerebrovascular disease, liver disease, renal disease, diabetes, chronic obstructive pulmonary disease (COPD), hypertension, obesity, cancers, neuropsychiatric conditions] were assessed from longitudinal data...

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Non-human primates (NHPs) are the most relevant model of Acquired Immunodeficiency Syndrome (AIDS) and neuroAIDS, being of great importance in explaining the pathogenesis of HIV-induced nervous system damage. Simian Immunodeficiency Virus (SIV)/ Simian-Human Immunodeficiency Virus (SHIV)-infected monkeys have provided evidence of complex interactions between the virus and host that include host immune response, viral genetic diversity, and genetic susceptibility, which may explain virus-associated central nervous system (CNS) pathology and HIV-associated neurocognitive disorders (HAND)...

INTRODUCTION: Moleac (MLC) 901 is a traditional Chinese medication approved by the Sino Food and Drug Administration in 2001 for treating stroke. This study aims to analyze the efficacy of MLC901 in animal stroke models after medial cerebral artery occlusion (MCAO). METHODS: Literature selection was performed according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) 2015. Inclusion criteria for the experimental studies were the use of animal models, publication in English between 1990 and 2020, information regarding the intervention technique used, and outcomes regarding the efficacy of MLC901 administration...

OBJECTIVE: People with human immunodeficiency virus (HIV) (PWH) have increased prevalence of multimorbidity and frailty at younger ages compared to the general population. This study investigated individual and combinatorial effects of neuropsychiatric and medical comorbidities as predictors of frailty in PWH. DESIGN: Analysis of data from the National NeuroAIDS Tissue Consortium, a longitudinal observational cohort. METHODS: 524 PWH over age 40 were classified using Fried's Frailty criteria...

OBJECTIVE: Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis's anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH. METHODS: 263 individuals were categorized into four groups: HIV- non-cannabis users (n = 65), HIV+ non-cannabis users (n = 105), HIV+ moderate cannabis users (n = 62), and HIV+ daily cannabis users (n = 31)...

HIV or SIV infection causes myelodysplasia, anemia and accumulation of inflammatory monocytes (CD14+ CD16+ ), through largely unknown cellular and molecular pathways. The mouse cells thought to be equivalent to human CD14+ CD16+ cells are CD11b+ Gr1+ myeloid-derived suppressive cells (MDSC). We used HIV transgenic (Tg) mouse models to study MDSC, namely CD4C/Nef Tg mice expressing nef in dendritic cells (DC), pDC, CD4+ T and other mature and immature myeloid cells and CD11c/Nef Tg mice with a more restricted expression, mainly in DC and pDC...

OBJECTIVES: NMDA glutamatergic receptors are heteromeric receptors with various subunits. GluN2A and GluN3A subunits specify the functional heterogeneity of NMDA receptors. These subunits play a key role in the induction of LTP and synaptic plasticity. Note that, the function of NMDA subunits has interaction with the mechanism of morphine. On the other hand, NeuroAid is a Chinese traditional medicine with neuroprotective and anti-apoptotic effects. In this study, we aimed to investigate the effect of morphine and NeuroAid on expression levels of GluN2A and GluN3A in the hippocampus and striatum of rats...