Ramesh Kumar Athi Kumar

Traumatic damage to the spinal cord (SCI) frequently leads to irreversible neurological deficits, which may be related to apoptotic neurodegeneration in nerve tissue. The MLC901 treatment possesses neuroprotective and neuroregenerative activity. This study aimed to explore the regenerative potential of MLC901 and the molecular mechanisms promoting neurogenesis and functional recovery after SCI in rats. A calibrated forceps compression injury for 15 s was used to induce SCI in rats, followed by an examination of the impacts of MLC901 on functional recovery. The Basso, Beattie, and Bresnahan (BBB) scores were utilized to assess neuronal functional recovery; H&E and immunohistochemistry (IHC) staining were also used to observe pathological changes in the lesion area. Somatosensory Evoked Potentials (SEPs) were measured using the Nicolet^® Viking Quest™ apparatus. Additionally, we employed the Western blot assay to identify PI3K/AKT/GSK-3β pathway-related proteins and to assess the levels of GAP-43 and GFAP through immunohistochemistry staining. The study findings revealed that MLC901 improved hind-limb motor function recovery, alleviating the pathological damage induced by SCI. Moreover, MLC901 significantly enhanced locomotor activity, SEPs waveform, latency, amplitude, and nerve conduction velocity. The treatment also promoted GAP-43 expression and reduced reactive astrocytes (GFAP). MLC901 treatment activated p-AKT reduced p-GSK-3β expression levels and showed a normalized ratio (fold changes) relative to β-tubulin. Specifically, p-AKT exhibited a 4-fold increase, while p-GSK-3β showed a 2-fold decrease in T rats compared to UT rats. In conclusion, these results suggest that the treatment mitigates pathological tissue damage and effectively improves neural functional recovery following SCI, primarily by alleviating apoptosis and promoting neurogenesis. The underlying molecular mechanism of this treatment mainly involves the activation of the PI3K/AKT/GSK-3β pathway.

Background: Resting-state functional magnetic resonance imaging (rs-fMRI) can evaluate brain functional connectivity without requiring subjects to perform a specific task. This rs-fMRI is very useful in patients with cognitive decline or unable to respond to tasks. However, long scan durations have been suggested to measure connectivity between brain areas to produce more reliable results, which are not clinically optimal. Therefore, this study aims to evaluate a shorter scan duration and compare the scan duration of 10 and 15 min using the rs-fMRI approach. Methods: Twenty-one healthy male and female participants (seventeen right-handed and four left-handed), with ages ranging between 21 and 60 years, were recruited. All participants underwent both 10 and 15 min of rs-fMRI scans. The present study evaluated the default mode network (DMN) areas for both scan durations. The areas involved were the posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), left inferior parietal cortex (LIPC), and right inferior parietal cortex (RIPC). Fifteen causal models were constructed and inverted using spectral dynamic causal modelling (spDCM). The models were compared using Bayesian Model Selection (BMS) for group studies. Result: The BMS results indicated that the fully connected model was the winning model among 15 competing models for both 10 and 15 min scan durations. However, there was no significant difference in effective connectivity among the regions of interest between the 10 and 15 min scans. Conclusion: Scan duration in the range of 10 to 15 min is sufficient to evaluate the effective connectivity within the DMN region. In frail subjects, a shorter scan duration is more favourable.

Spinal cord injury (SCI) is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions. Its pathophysiology comprises acute and chronic phases and incorporates a cascade of destructive events such as ischemia, oxidative stress, inflammatory events, apoptotic pathways and locomotor dysfunctions. Many therapeutic strategies have been proposed to overcome neurodegenerative events and reduce secondary neuronal damage. Efforts have also been devoted in developing neuroprotective and neuro-regenerative therapies that promote neuronal recovery and outcome. Although varying degrees of success have been achieved, curative accomplishment is still elusive probably due to the complex healing and protective mechanisms involved. Thus, current understanding in this area must be assessed to formulate appropriate treatment modalities to improve SCI recovery. This review aims to promote the understanding of SCI pathophysiology, interrelated or interlinked multimolecular interactions and various methods of neuronal recovery i.e., neuroprotective, immunomodulatory and neuro-regenerative pathways and relevant approaches.