Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.

Simple Protocol for the Micropropagation of Teak(Tectona grandis Linn.)in Semi-Solid and Liquid Media in RITA^(█) Bioreactors and ex Vitro Rooting

In Latin America the forestry of exotic species such as teak has been increasing in recent decades, due to their advantages in wood quality, rapid growth;and the relative ease of producing clones and their multiplication with respect to native species. Therefore, there is great interest in developing larger-scale propagation strategies that reduce costs and intensive manual labor. Culture in liquid media with temporary immersion and the semi-automation of the system has raised expectations for large-scale micropropagation. We report a protocol for teak, which reuses the primary explants in several culture cycles in semi-solid medium to produce nodal explants for the multiplication phase in temporary immersion bioreactors (RITA®). The control of factors such as cytokinin concentration, explants density, immersion frequencies and culture duration was analyzed. The number of shoots increased with 0.5 mg·l-1 of BA (6-Benzyladenine), alone or in combination with 0.5 mg·l-1 of Kinetin, with 2 daily immersions of 1 minute each;however, these shoots showed a high degree of hyperhydricity. When 0.05 mg·l-1 of BA was used with 1 immersion of 1 minute every 2 days, the hyperhydricity decreased. Although the number of shoots was lower, they showed good length to be used during multiplication and rooting ex vitro. Our results suggest that teak micropropagation can be simplified in two phases in vitro, the establishment and multiplication;followed by rooting ex vitro and acclimatization. This would imply a reduction in production costs, since most of the multiplication would take place in RITA®containers.

Brain metabolism in patients with vegetative state after post-resuscitated hypoxic-ischemic brain injury： statistical parametric mapping analysis of F-18 fluorodeoxyglucose positron emission tomography

Background Hypoxic-ischemic brain injury （HIBI） after cardiopulmonary resuscitation is one of the most devastating neurological conditions that causing the impaired consciousness. However, there were few studies investigated the changes of brain metabolism in patients with vegetative state （VS） after post-resuscitated HIBI. This study aimed to analyze the change of overall brain metabolism and elucidated the brain area correlated with the level of consciousness （LOC） in patients with VS after post-resuscitated HIBI. Methods We consecutively enrolled 17 patients with VS after HIBI, who experienced cardiopulmonary resuscitation. Overall brain metabolism was measured by F-18 fluorodeoxyglucose positron emission tomography （F-18 FDG PET） and we compared regional brain metabolic patterns from 17 patients with those from 15 normal controls using voxel-by-voxel based statistical parametric mapping analysis. Additionally, we correlated the LOC measured by the JFK-coma recovery scale-revised of each patient with brain metabolism by covariance analysis. Results Compared with normal controls, the patients with VS after post-resuscitated HIBI revealed significantly decreased brain metabolism in bilateral precuneus, bilateral posterior cingulate gyrus, bilateral middle frontal gyri, bilateral superior parietal gyri, bilateral middle occipital gyri, bilateral precentral gyri （PFEw correctecd 〈0.0001 ）, and increased brain metabolism in bilateral insula, bilateral cerebella, and the brainstem （PFEWcorrectecd 〈0.0001 ）. In covariance analysis, the LOC was significantly correlated with brain metabolism in bilateral fusiform and superior temporal gyri （P uncorrected 〈0.005）. Conclusions Our study demonstrated that the precuneus, the posterior cingulate area and the frontoparietal cortex, which is a component of neural correlate for consciousness, may be relevant structure for impaired consciousness in patient with VS after post-resuscitated HIBI. In post-resuscitated HIBI, measurement of brain metabolism using PET images may be helpful for investigating the brain function that cannot be obtained by morphological imaging and can be used to assess the brain area responsible for consciousness.

Voxel-based statistical analysis of cerebral glucose metabolism in patients with permanent vegetative state after acquired brain injury

Background Permanent vegetative state is defined as the impaired level of consciousness longer than 12 months after traumatic causes and 3 months after non-traumatic causes of brain injury. Although many studies assessed the cerebral metabolism in patients with acute and persistent vegetative state after brain injury, few studies investigated the cerebral metabolism in patients with permanent vegetative state. In this study, we performed the voxel-based analysis of cerebral glucose metabolism and investigated the relationship between regional cerebral glucose metabolism and the severity of impaired consciousness in patients with permanent vegetative state after acquired brain injury.Methods We compared the regional cerebral glucose metabolism as demonstrated by F-18 fluorodeoxyglucose positron emission tomography from 12 patients with permanent vegetative state after acquired brain injury with those from 12 control subjects. Additionally, covariance analysis was performed to identify regions where decreased changes in regional cerebral glucose metabolism significantly correlated with a decrease of level of consciousness measured by JFK-coma recovery scare. Statistical analysis was performed using statistical parametric mapping.Results Compared with controls, patients with permanent vegetative state demonstrated decreased cerebral glucose metabolism in the left precuneus, both posterior cingulate cortices, the left superior parietal lobule （Pcorrected 〈0.001）, and increased cerebral glucose metabolism in the both cerebellum and the right supramarginal cortices （Pcorrected 〈0.001）. In the covariance analysis, a decrease in the level of consciousness was significantly correlated with decreased cerebral glucose metabolism in the both posterior cingulate cortices （Puncorrected 〈0.005）.Conclusion Our findings suggest that the posteromedial parietal cortex, which are part of neural network for consciousness, may be relevant structure for pathophysiological mechanism in patients with permanent vegetative state after acquired brain injury.