Harnessing the therapeutic potential of mesenchymal stem/stromal cell-derived extracellular vesicles as a novel cell-free therapy for animal models of multiple sclerosis.

Multiple sclerosis (MS) is a chronic, neuroinflammatory, and demyelinating disease of the central nervous system (CNS). Current treatments offer only limited relief from symptoms, and there is no cure. Mesenchymal stem/stromal cells (MSCs) have demonstrated therapeutic potential for MS. However, their clinical application faces challenges, including immune rejection and the potential for tumor formation. Recent studies suggest that MSCs exert their effects through extracellular vesicles (EVs) released from the cells, rather than direct cellular engraftment or differentiation. This discovery has sparked interest in the potential of MSC-derived EVs as a cell-free therapy for MS. This review explores the existing literature on the effects of MSC-EVs in animal models of MS. Administration of MSC-EVs from various tissue sources, such as bone marrow, adipose tissue, and umbilical cord, was found to reduce clinical scores and slow down disease progression in experimental autoimmune encephalomyelitis (EAE), the primary mouse model of MS. The mechanisms involved immunomodulation through effects on T cells, cytokines, CNS inflammation, and demyelination. Although the impact on CNS repair markers remained unclear, MSC-EVs exhibited the potential to modulate neuroinflammation and suppress harmful immune responses in EAE. Further studies are still required, but MSC-EVs demonstrate promising therapeutic effects for MS and warrant further exploration as a novel treatment approach.

Dipeptide mimetic of BDNF ameliorates motor dysfunction and striatal apoptosis in 6-OHDA-induced Parkinson's rat model: Considering Akt and MAPKs signaling.

Parkinson's disease (PD) is a progressive and debilitating neurodegenerative disorder associated with motor and non-motor complaints. Dysregulation of neurotrophic factors and related signaling cascades have been reported to be common events in PD which is accompanied by dopaminergic (DA) neuron demise. However, the restoration of neurotrophic factors has several limitations. Bis-(N-monosuccinyl-L-methionyl-L-serine) heptamethylenediamide (BHME) is a dipeptide mimetic of brain-derived neurotrophic factor (BDNF) with reported anti-oxidant and neuroprotective effects in several experimental models. The current study has investigated the effect of BHME on 6-hydroxydopamine (6-OHDA)-caused motor anomalies in Wistar rats. In this regard, rats were treated daily with BHME (0.1 or 1 mg/kg) 1 h after 6-OHDA-caused damage until the twelfth day. Afterwards, motor behavior and DA neuron survival were evaluated via behavioral tests and immunohistochemistry (IHC) staining, respectively. Moreover, the activity of Akt, mitogen-activated protein kinases (MAPKs) family, and Bax/Bcl-2 ratio were evaluated by Western blotting. Our results indicated that BHME prevents motor dysfunction and DA cell death following 6-OHDA injection, and this improvement was in parallel with an enhancement in Akt activity, decrement of P38 phosphorylation, along with a reduction in Bax/Bcl-2 ratio. In conclusion, our findings indicated that BHME, as a mimetic of BDNF, can be considered for further research and is a promising therapeutic agent for PD therapy.

Development of Acute Transverse Myelitis following COVID-19 Infection: A Review on the Potential Pathways.

BACKGROUND: Acute transverse myelitis (ATM) is a rare neurological disorder in adults characterized by localized inflammation of gray and white matter in one or more contiguous spinal cord segments in the absence of a compressive injury. Several reports have connected the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the pathophysiology of ATM. SUMMARY: Direct invasion of the spinal cord, cytokine storm, or an autoimmune response are the possible pathways by which the SARS-CoV-2 virus can affect the spinal cord and lead to ATM. Direct invasion is facilitated by the presence of angiotensin-converting enzyme 2 (ACE2) receptors on the membranes of the spinal cord neurons. Cytokine storm syndrome could be derived from elevated levels of several immunological factors following severe involvement with coronavirus disease 2019 (COVID-19). Finally, autoimmune responses can cause post-infectious ATM through several hypothesized processes, including molecular mimicry, epitope spreading, bystander activation, and polyclonal B-cell activation. KEY MESSAGES: COVID-19-induced ATM is mostly a longitudinally-extensive ATM (LEATM), in which more spinal cord segments are damaged, which results in a worse sequel compared to short-segment ATM. Therefore, it is suggested that COVID-19 patients, particularly severe cases, be followed up for a probable incidence of ATM, even long after recovery from the disease and elimination of the virus from the host, because an early diagnosis and effective therapy may stop the spread of inflammation to adjacent segments.

Intranasal insulin improves mitochondrial function and attenuates motor deficits in a rat 6-OHDA model of Parkinson's disease.

AIMS: Experimental and clinical evidences demonstrate that common dysregulated pathways are involved in Parkinson's disease (PD) and type 2 diabetes. Recently, insulin treatment through intranasal (IN) approach has gained attention in PD, although the underlying mechanism of its potential therapeutic effects is still unclear. In this study, we investigated the effects of insulin treatment in a rat model of PD with emphasis on mitochondrial function indices in striatum. METHODS: Rats were treated with a daily low dose (4IU/day) of IN insulin, starting 72 h after 6-OHDA-induced lesion and continued for 14 days. Motor performance, dopaminergic cell survival, mitochondrial dehydrogenases activity, mitochondrial swelling, mitochondria permeability transition pore (mPTP), mitochondrial membrane potential (Δψm ), reactive oxygen species (ROS) formation, and glutathione (GSH) content in mitochondria, mitochondrial adenosine triphosphate (ATP), and the gene expression of PGC-1α, TFAM, Drp-1, GFAP, and Iba-1 were assessed. RESULTS: Intranasal insulin significantly reduces 6-OHDA-induced motor dysfunction and dopaminergic cell death. In parallel, it improves mitochondrial function indices and modulates mitochondria biogenesis and fission as well as activation of astrocytes and microglia. CONCLUSION: Considering the prominent role of mitochondrial dysfunction in PD pathology, IN insulin as a disease-modifying therapy for PD should be considered for extensive research.