Background: Negative geotaxis (NG) is an important parameter, commonly used in study of different CNS diseases and neurodevelopmental disorders. Neurobehavioural change following brain injury was easily identified by negative geotaxis. Purpose: Although NG is evaluated in the settings of ASD, most of the studies are conducted for short duration (1-3 day) and the overall trend of acquisition of NG is not evaluated. In this context, we wanted to evaluate the trend of acquisition of negative geotaxis as a behavioural marker of autism in Valproic acid (VPA) model of ASD. Methods: Dams in the VPA group were treated with intraperitoneal injections of VPA 600 mg/kg single dose on gestational day 12.5, while the control animals received normal saline of similar volume. Developmental parameters {body weight (PND 8, 10 & 12), body length (PND 4, 5, 6 8, 10), eye opening (PND 10, 12, 14, 15 and 16) and motor development (grid walking test on PND 20)} were monitored. Negative geotaxis test was performed at PND 6, 10, 15 and 17. Results: The results of the present experiments demonstrate that VPA exposed rats exhibited delayed developmental parameters, aberration of the pattern of acquisition of negative geotaxis, enhanced negative geotaxis in early postnatal period (PND 6) and enhanced negative geotaxis in absence of visual clues (PND 17). Conclusion: NG can be a valuable biomarker in early detection of autistic behavior and in absence of visual clues. The abberant negative geotaxis developmental pattern can serve as a marker to detect ASD. Thus NG can serve as an important early age biomarker of ASD. Further studies are required to validate this finding.

Cirrhosis is a severe form of liver fibrosis that results in the irreversible replacement of liver tissue with scar tissue in the liver. Environmental toxicity, infections, metabolic causes, or other genetic factors including autoimmune hepatitis can lead to chronic liver injury and can result in inflammation and fibrosis. This activates myofibroblasts to secrete ECM proteins, resulting in the formation of fibrous scars on the liver. Fibrosis regression is possible through the removal of pathophysiological causes as well as the elimination of activated myofibroblasts, resulting in the reabsorption of the scar tissue. To date, a wide range of antifibrotic therapies has been tried and tested, with varying degrees of success. These therapies include the use of growth factors, cytokines, miRNAs, monoclonal antibodies, stem-cell-based approaches, and other approaches that target the ECM. The positive results of preclinical and clinical studies raise the prospect of a viable alternative to liver transplantation in the near future. The present review provides a synopsis of recent antifibrotic treatment modalities for the treatment of liver cirrhosis, as well as a brief summary of clinical trials that have been conducted to date.

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The imbalance between excitatory and inhibitory neurotransmitters is explicitly related to the pathophysiology of autism spectrum disorder (ASD). The role of an NMDA receptor antagonist, dextromethorphan, was studied in ameliorating the ASD-like symptoms by regulating the excitatory and inhibitory imbalance using the valproic acid (VPA) model of ASD. Female Wistar rats were administered VPA [600 mg/kg on embryonic day ED-12.5] through intraperitoneal (ip) injection to induce ASD in pups. Autistic pups were then given dextromethorphan (10, 15, and 30 mg/kg; ip) and risperidone (2.5 mg/kg; ip) from PND 23 to 43 in different groups. Behavioral tests (three chamber sociability, self-grooming, Morris water maze, elevated plus maze, open field, rotarod, grip strength), oxidative stress and inflammatory markers, histological evaluation (H&E, Nissil staining), and NMDA and ERK1/2 expression by immunohistochemistry and RT-PCR were done. The in silico modeling of dextromethorphan against PPDA, TCN-201, MK-22, EVT-101 on NMDA receptors was also performed. Dextromethorphan (30 mg/kg) rescued the impaired behavioral patterns including social excitability, hyperactivity, repetitive and restricted behaviors as well as mitigation of the memory and motor coordination. The levels of various oxidative stress markers (GSH, SOD, catalase, MDA) and inflammatory markers (IL-1β, IL-6, IL-10, TNF-α) were ameliorated by different doses of dextromethorphan. It also reduced the neuronal injury score and rescued the overly expressed pERK1/2 and NMDA signaling in both the prefrontal cortex and hippocampus of the autistic pups. In silico results showed favorable binding of dextromethorphan against TCN-201 and MK-22 binding sites. The present study provided experimental evidence for the potential therapeutic role of dextromethorphan in attenuating autism symptomatology in the ASD model of rats. Thus, modulation of the glutamatergic signaling can be a potential target for ASD treatment.

Aim: The aim of the study was to evaluate the neuroprotective effect of bone marrow stem cell secretome in the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease. Materials & methods: Secretome prepared from mesenchymal stem cells of 3-month-old rats was injected daily for 7 days between days 7 and 14 after 6-OHDA administration. After 14 days, various neurobehavioral parameters were conducted. These behavioral parameters were further correlated with biochemical and molecular findings. Results & conclusion: Impaired neurobehavioral parameters and increased inflammatory, oxidative stress and apoptotic markers in the 6-OHDA group were significantly modulated by secretome-treated rats. In conclusion, mesenchymal stem cells-derived secretome could be further explored for the management of Parkinson's disease.