Journal of Neuroscience Research最新文献

Despite significant advancements in achieving high recanalization rates (80%–90%) for large vessel occlusions through mechanical thrombectomy, the issue of “futile recanalization” remains a major clinical challenge. Futile recanalization occurs when over half of patients fail to experience expected symptom improvement after vessel recanalization, often resulting in severe functional impairment or death. Traditionally, this phenomenon has been attributed to inadequate blood flow and reperfusion injury. More recently, ongoing neuronal death after reperfusion, which leads to the progression of the ischemic penumbra into the core infarct, has been termed “futile reperfusion.” This review explores the complex role of autophagy mechanisms in futile reperfusion following ischemic stroke, with a focus on its relationship to neuronal survival. We also examine the regulation of autophagic activity by epigenetic mechanisms. By investigating autophagy's role in ischemic stroke, we aim to identify novel pathways for precision treatment.

Parkinson's Disease (PD) is a neurodegenerative disorder marked by the depletion of dopaminergic neurons. Recent studies highlight the gut-liver-brain (GLB) axis and its role in PD pathogenesis. The GLB axis forms a dynamic network facilitating bidirectional communication between the gastrointestinal tract, liver, and central nervous system. Dysregulation within this axis, encompassing gut dysbiosis and microbial metabolites, is emerging as a critical factor influencing PD progression. Our understanding of PD was traditionally centered on neurodegenerative processes within the brain. However, examining PD through the lens of the GLB axis provides new insights. This review provides a comprehensive analysis of microbial metabolites, such as short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), kynurenine, serotonin, bile acids, indoles, and dopamine, which are integral to PD pathogenesis by modulation of the GLB axis. Our extensive research included a comprehensive literature review and database searches utilizing resources such as gutMGene and gutMDisorder. These databases have been instrumental in identifying specific microbes and their metabolites, shedding light on the intricate relationship between the GLB axis and PD. This review consolidates existing knowledge and underscores the potential for targeted therapeutic interventions based on the GLB axis and its components, which offer new avenues for future PD research and treatment strategies. While the GLB axis is not a novel concept, this review is the first to focus specifically on its role in PD, highlighting the importance of integrating the liver and microbial metabolites as central players in the PD puzzle.

Neurological diseases are central nervous system (CNS) disorders affecting the whole body. Early diagnosis of the diseases is difficult due to the lack of disease-specific tests. Adding new biomarkers external to the CNS facilitates the diagnosis of neurological diseases. In this respect, the retina has a common embryologic origin with the CNS. Retinal imaging technologies including optical coherence tomography (OCT) can be used in the understanding and processual monitoring of neurological diseases. Retinal imaging has been recently recognized as a potential source of biomarkers for neurological diseases, increasing the number of studies in this direction. In this review, the association of retinal abnormalities with Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD) is explained. Structural and functional abnormalities in retina as a predictive marker may facilitate early diagnosis of diseases. Although not all retinal abnormalities are predictive of neurologic diseases, changes in the retinal layers including retinal pigment epithelium and plexiform layers should suggest the risk of PD, MS, ALS, and AD.

Lateralization of motor behavior, a common phenomenon in humans and several species, is modulated by the basal ganglia, a site pointed out for the interhemispheric differences related to lateralization. Our study aims to shed light on the potential role of the striatonigral D1 receptor in functional asymmetry in normal conditions through neurochemical and behavioral means. We found that D1 receptor activation and D1/D3 receptor coactivation in striatonigral neurons leads to more cAMP production by adenylyl cyclase in the striatum and GABA release in their terminals in the right hemisphere compared to the left. These differences are linked to a higher receptor sensitivity and potentially a better coupling of G_olf proteins. When we assessed motor behavior through intranigral injection of the D1 receptor agonist SKF 38393 in the left or right substantia nigra, we found higher contralateral circling when injected on the right side. Thus, differences in motor activity correlate with neurochemical data, indicating that D1 receptor signaling plays a significant role in motor asymmetry.

Remote ischemic conditioning (RIC) has attracted considerable attention as a brain protection strategy, although its impact remains unclear. Hypothermia is the most effective strategy in experimental transient cerebral ischemia. Therefore, we compared the efficacy of RIC, hypothermia, and no treatment on cerebral ischemia. We assessed the effects of both permanent and transient middle cerebral artery occlusion (MCAO) for 45 min in male mice. Brain hemodynamics were monitored during and after the procedure via 2D color-coded ultrasound imaging. Ischemic lesions on magnetic resonance imaging (MRI)–diffusion-weighted imaging (DWI), early breakdown of microtubule-associated protein 2 (MAP2), expression levels of inflammatory cytokines by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), and neurological signs and infarct volume were examined. In permanent MCAO, RIC increased cerebral blood flow (CBF) in the peri-infarct area, reduced early lesions on MRI–DWI, decreased early MAP2 breakdown, and lowered infarct volume compared with no treatment. However, hypothermia only showed a protective effect against neurological signs. In contrast, in transient MCAO, both RIC and hypothermia reduced the expression of inflammatory cytokines, mitigated MAP2 breakdown, and reduced infarct volume to a similar extent compared with no treatment. In conclusion, although RIC proved to be more effective than hypothermia in permanent MCAO, the protective effects of RIC and hypothermia were comparable in transient cerebral ischemia. Thus, RIC could be a promising strategy for brain protection against cerebral ischemia.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder traditionally characterized by the selective loss of medium spiny neurons in the basal ganglia. However, it has become apparent that white matter injury and oligodendrocyte dysfunction precede the degeneration of medium spiny neurons, garnering interest as a key pathogenic mechanism of HD. Oligodendrocytes are glial cells found within the central nervous system involved in the production of myelin and the myelination of axons. Myelin is a lipid-rich sheath that wraps around axons, facilitating signal conduction and neuronal viability. The degeneration of myelin hinders effective communication and leaves neurons vulnerable to external damage and subsequent degeneration. Abnormalities in oligodendrocyte maturation have been established in the HD human brain, however, investigations into the underlying dysfunction of human oligodendrocytes in HD are limited. This review will detail the involvement of oligodendrocytes and white matter damage in HD. Recent developments in modeling human-specific oligodendrocyte pathology in HD will be discussed, with a particular focus on emerging somatic cell reprogramming approaches.