Biology subjects

Jaberi, R.

Publications and source records attributed to Jaberi, R..

4 recordsLinked to original sources

bioRxiv2026

A Neurocompliant Ionic Conductive Hydrogel Orchestrates Glial and Vascular Remodeling to Mitigate Traumatic Brain Injury

Developing conductive scaffolds for neural regeneration is often hindered by the cytotoxicity and mechanical mismatch inherent to conventional electronic fillers. Here, we report an ultrasoft ionically conductive hydrogel engineered by grafting choline-based bioionic liquids (BIL) onto fish gelatin (FiBGel). Systematic optimization yields brain-mimetic conductivity (0.25-0.68 S/m), elastic moduli (0.6-0.9 kPa), and physiological water content (72-81%). In 3D culture, the matrix drives spontaneous neurogenesis, achieving ~90% MAP2+ neurons with robust calcium signaling, while concurrently supporting endothelial network formation. We report the first intracerebral administration of a BIL hydrogel, demonstrating remarkable biocompatibility and immunomodulation. In a traumatic brain injury model, a single FiBGel dose halves reactive astrogliosis, enhances cortical revascularization, and limits lesion cavity expansion. Leveraging an FDA-recognized micronutrient, FiBGel offers a translatable strategy that integrates neuromechanics, conductivity, immune modulation, and vascular support within one injectable scaffold for minimally invasive treatment of brain injuries.

neuroscience↗

bioRxiv2026

Concussive Injury in Human Forebrain Organoids Alters Neurogenesis and Neuroimmune Signaling

Traumatic brain injury (TBI) is a major cause of long-term neurological disability, yet the mechanisms underlying human-specific injury responses remain poorly understood. Rodent models of TBI have yielded significant insights into mechanisms and pathophysiology of TBI but may not capture human-specific developmental and molecular responses. Here, we establish a human forebrain organoid (hFBO) injury paradigm to examine developmental stage and region-specific responses to concussive injury. Dorsal and ventral hFBOs, enriched in glutamatergic and GABAergic neurons, respectively, showed progressive physiological maturation with rudimentary firing characteristics at 80 days in vitro (DIV) and spontaneous synaptic activity by 150 DIV. Injury to dorsal and ventral hFBOs at 25 DIV, when neural progenitors dominate, caused cell death that scaled with severity and increased expression of neural proliferation markers and TLR4/NF-{kappa}B associated neuroimmune signaling. Injury to physiologically mature organoids at 150 DIV produced severity-dependent acute intracellular calcium dysregulation. Together, these findings establish a human organoid-based platform that captures developmental stage-dependent neurogenic, molecular, and cellular dysfunction in responses to concussive injury.

neuroscience↗

bioRxiv2026

Neuronal Toll-like Receptor-4 regulation of Matrix Metalloproteinase-9 Activity Mediates Dentate Circuit Dysfunction after Traumatic Brain Injury

Neuroinflammatory pathways activated by traumatic brain injury (TBI) are critical mediators of long-term neurological dysfunction and represent promising therapeutic targets. Toll-like receptor 4 (TLR4), an innate immune receptor, was previously shown to contribute to increased seizure susceptibility and cognitive deficits in rats after lateral fluid percussion injury (FPI). However, the cellular and molecular mechanisms underlying TLR4-mediated circuit dysfunction early after brain injury are not fully understood. In this study, we define a cell- and circuit-specific neuroimmune-enzyme effector signaling axis that mediates early post-TBI circuit dysfunction in the hippocampal Dentate Gyrus (DG). Using ex vivo electrophysiology in rat and mouse models one-week after brain injury, we demonstrate that neuronal TLR4 signaling regulates both excitatory and inhibitory synaptic inputs to dentate granule cells (DGC). Collectively, pharmacological inhibition of TLR4 in rats and cell-type-specific deletion of TLR4 in mice show that neuronal TLR4 mediates injury-driven increase in DGC excitatory input frequency and relies on downstream activation of Matrix Metalloproteinase-9 (MMP-9). In contrast, TLR4 signaling contributed to decrease in inhibitory current frequency after injury, but independent of MMP-9, revealing a mechanistic divergence. Systemic inhibition of either TLR4 signaling or MMP-9 activity in rats within 24 hours after injury reduced network hyperexcitability and improved long-term potentiation (LTP) in the DG measured in vivo one-week after injury. Either TLR4 or MMP-9 inhibition early after injury effectively attenuated spatial memory deficits in a Barnes maze task one-month post-injury. Paradoxically, in sham controls, inhibition of TLR4 increased frequency of both excitatory and inhibitory inputs to DGCs and augmented network excitability, without altering MMP-9 levels, identifying context-dependent roles for TLR4 signaling. Together, these results identify a novel TLR4-MMP-9 axis as a key driver of early post-TBI dentate gyrus circuit dysfunction and behavioral deficits.

neuroscience↗

bioRxiv2023

Transplanted Autologous Neural Stem Cells Show Promise in Restoring Motor Function in Monkey Spinal Cord Injury

Spinal cord injury (SCI) is a devastating condition that can result in permanent loss of motor and sensory function. In recent years, transplantation of neural stem cells (NSCs) has emerged as a promising therapeutic approach for SCI. However, adult NSCs residing in the central nervous system (CNS) show promise for cell-replacement therapy in neurodegenerative disorders. In this study, we aimed to investigate the efficacy of transplanting autologous NSCs isolated from the subventricular zone (SVZ-NSCs) into a spinal cord injury model in Rhesus monkeys. We induced SCI in eight Rhesus monkeys and then transplanted SVZ-NSCs into the injury site. Behavioral assessments and magnetic resonance imaging (MRI) were performed to evaluate the functional and structural recovery of the spinal cord. Histological analyses were also performed to assess the survival and differentiation of the transplanted cells. SVZ-NSCs were capable of expressing SOX2, Nestin, and GFAP in addition to self-renewing and spontaneous differentiation in vitro. The monkeys showed sensory and motor function recovery, spinal tract regeneration, and partial reconstruction of the spinal cord. Positive Reinforcement Training confirmed no adverse effects from the isolation procedure. Our findings suggest that NSCs transplantation could be a promising therapeutic approach for SCI in humans, and further studies are warranted to investigate its potential for clinical translation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=159 SRC="FIGDIR/small/539673v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@1f9257forg.highwire.dtl.DTLVardef@cbd0aorg.highwire.dtl.DTLVardef@4ef324org.highwire.dtl.DTLVardef@13ce48b_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗