Intracerebroventricular Administration of hNSCs Improves Neurological Recovery after Cardiac Arrest in Rats.

Irreversible brain injury and neurological dysfunction induced by cardiac arrest (CA) have long been a clinical challenge due to lack of effective therapeutic interventions to reverse neuronal loss and prevent secondary reperfusion injury. The neuronal regenerative potential of neural stem cells (NSCs) provides a possible solution to this clinical deficit. We investigated the neuronal recovery potential of human neural stem cells (hNSCs) via intracerebroventricular (ICV) xenotransplantation after CA in rats and the effects of transplanted NSCs on the proliferation and migration of endogenous NSCs. Outcome measures included neurological functional recovery measured by neurological deficit score (NDS), electrophysiologic analysis of EEG, and assessment of proliferation and migration at the cellular level and the Wnt/ß-catenin pathway at the molecular level. Neurological functional assessment based on aggregate neurological deficit score (NDS) showed better recovery of function after hNSCs therapy (P < 0.05). Tracking of stem cells' proliferation with Ki67 antibody suggested that the NSCs group had more prominent proliferation compared to control group (number of Ki67+ cells, Control VS. NSC: 89.0 ± 31.6 VS. 352.7 ± 97.3, P < 0.05). In addition, cell migration tracked by Dcx antibody showed more Dcx + cells migrated to the far distance zone from SVZ in the treatment group (P < 0.05). Further immunofluorescence staining confirmed that the expression of the Wnt signaling pathway protein (ß-catenin) was upregulated in the NSC group (P < 0.05). ICV delivery of hNSCs promotes endogenous NSC proliferation and migration and ultimately enhances neuronal survival and neurological functional recovery. Wnt/ß-catenin pathway may be involved in the initiation and maintenance of this enhancement.Graphical abstract.

Effects of plant-derived analgesic compounds sinomenine and salvinorin A in infant rats.

OBJECTIVE: Premature and ill neonates undergo painful but medically necessary procedures while hospitalized. Although opiate drugs are administered as analgesics, problems associated with their side effects, tolerance, and potential dependence necessitate research into alternative pain-relieving medications. Here we test two plant-derived compounds in infant rats: sinomenine, which targets the Mas-related G-protein-coupled receptor member X2 opioid receptor; and salvinorin A, which is a κ opioid receptor agonist. In adult animals both sinomenine and salvinorin A are analgesic, but neither has been tested in infants. METHODS: We used the formalin and thermal plantar tests in rats 7 and 21 days of age (PN7 and PN21) for behavioral signs of pain. In addition, brain sections were stained using Fos immunohistochemistry to examine patterns of brain activation in the midbrain periaqueductal gray and the paraventricular nucleus of the hypothalamus. RESULTS: Sinomenine was analgesic in both the formalin and thermal tests on animals 21 days of age. At PN7 only the highest dose elevated response latencies in the thermal test and there were no effects of sinomenine in the formalin test. Analysis of Fos expression in the sinomenine-treated animals showed no drug effect, in contrast to the behavioral results. Salvinorin A was analgesic in the formalin test only at the highest dose at 21 days of age but not in the thermal test at either age. CONCLUSION: The increased modest effectiveness of sinomenine in older animals and the minimum salvinorin A drug effect suggest that the compounds act on sites that develop during the preweaning period (sinomenine) or after weaning (salvinorin A).

Positron Emission Tomography After Ischemic Brain Injury: Current Challenges and Future Developments.

Positron emission tomography (PET) is widely used in clinical and animal studies, along with the development of diverse tracers. The biochemical characteristics of PET tracers may help uncover the pathophysiological consequences of cardiac arrest (CA) and ischemic stroke, which include cerebral ischemia and reperfusion, depletion of oxygen and glucose, and neuroinflammation. PubMed was searched for studies of the application of PET for "cardiac arrest," "ischemic stroke," and "targeted temperature management." Available studies were included and classified according to the biochemical properties involved and metabolic processes of PET tracers, and were summarized. The mechanisms of ischemic brain injuries were investigated by PET with various tracers to elucidate the pathological process from the initial decrease of cerebral blood flow (CBF) to the subsequent abnormalities in energy and oxygen metabolism, to the monitoring of inflammation. In general, the trends of cerebral blood flow and oxygen metabolism after ischemic attack are not unidirectional but closely related to the time point of injury and recovery. Glucose metabolism after injury showed significant differences in different brain regions whereas global cerebral metabolic rate of glucose (CMRglc) declined. PET monitoring of neuroinflammation shows comparable efficacy to immunostaining. The technology of PET targeting in brain metabolism and the development of tracers provide new tools to track and evaluate the brain's pathological changes after ischemic brain injury. Despite no existing evidence for an available PET-based prediction method, discoveries of new tracers are expected to provide more possibilities for the whole field.