Impairment of the blood brain barrier accelerates a negative ultraslow potential in the locust CNS

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 17, 2025

Abstract Insects provide useful models for investigating evolutionarily conserved mechanisms underlying electrical events associated with brain injury and death. Spreading depolarizations (SD) are transient that propagate through neuropil whereas the negative ultraslow potential (NUP) is sustained reflects accumulating damage in tissue. We used locust, Locusta migratoria , to investigate ion homeostasis at blood barrier (BBB) during SD NUP induced by treatment Na + /K -ATPase inhibitor, ouabain. found caused metabolic sodium azide, was a large reduction of K efflux BBB ganglia (= grey matter) but not connectives white matter). This accompanied increase tissue resistivity no conductance changes identified motoneuron dendrites neuropil. Males recovered more slowly from ouabain-induced SD, as previously described anoxic SD. Impairment functions pharmacologically cyclosporin A or DIDS, cutting nerve roots, accelerated NUP, thus promoting earlier frequent had effect on temporal parameters conclude onset recovery minimally affected NUP. suggest future research using tissue-specific genetic approaches Drosophila target molecular structures likely be fruitful. New Noteworthy Inhibition pump locust CNS causes repetitive spreading depolarization providing model investigation phenomena relevant human health. show impairment accelerates has impact trajectory events. Hence, rapid occur against background increasing neural damage.

Язык: Английский

Chemogenetic modulation in stroke recovery: A promising stroke therapy Approach

Brain stimulation, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Stroke remains a leading cause of long-term disability and mortality worldwide, necessitating novel therapeutic strategies to enhance recovery. Traditional rehabilitation approaches, including physical therapy pharmacological interventions, often provide limited functional improvement. Neuromodulation has emerged as promising strategy promote post-stroke recovery by enhancing neuroplasticity reorganization. Among various neuromodulatory techniques, chemogenetics, particularly Designer Receptors Exclusively Activated Drugs (DREADDs), offers precise, cell-type-specific, temporally controlled modulation neuronal glial activity. This review explores the mechanisms potential chemogenetic in stroke Preclinical studies have demonstrated that activation excitatory DREADDs (hM3Dq) neurons located within peri-infarct area or contralateral M1 been shown neuroplasticity, facilitate axonal sprouting, lead improved behavioral following stroke. Conversely, stimulation inhibitory (hM4Di) suppresses stroke-induced excitotoxicity, mitigates spreading depolarizations (PIDs), modulates neuroinflammatory responses. By targeting specific populations, chemogenetics enables phase-specific interventions-early inhibition minimize damage during acute phase late excitation plasticity phase. Despite its advantages over traditional neuromodulation such optogenetics deep brain stimulation, several challenges remain before can be translated into clinical applications. These include optimizing viral vector delivery, improving ligand specificity, minimizing off-target effects, ensuring receptor stability. Furthermore, integrating with existing strategies, brain-computer interfaces therapy, may facilitating adaptive neuroplasticity. Future research should focus on refining tools enable application. offering highly selective, reversible, minimally invasive approach, holds great for revolutionizing advancing personalized strategies.

Язык: Английский