Biology subjects

Barbay, S.

Publications and source records attributed to Barbay, S..

6 recordsLinked to original sources

bioRxiv2025

Controlled Release of Bone Morphogenetic Protein-2 Improves Motor Function After Traumatic Brain Injury in a Rat Model

Severe traumatic brain injury (TBI) is a life-threatening condition characterized by internal brain swelling and commonly treated using a two-stage surgical approach. The interval between surgeries, generally spaced weeks to months, is associated with secondary neurologic complications from leaving the brain unprotected. Hydrogels may reshape severe TBI treatment by enabling a single-stage surgical intervention, capable of being implanted at the initial surgery, remaining flexible to accommodate brain swelling, and calibrated to regenerate bone after brain swelling has subsided. The current study evaluated the use of a pentenoate-modified hyaluronic acid (PHA) polymer with thiolated devitalized tendon (TDVT) for calvarial bone regeneration in a rat TBI model. Additionally, PHA-TDVT hydrogels encapsulating microspheres containing bone morphogenetic protein-2 (BMP-2) were investigated to enhance bone regeneration. All hydrogel precursor formulations exhibited sufficient yield stress for surgical placement. The addition of TDVT to the crosslinked hydrogels increased the average compressive modulus. In vitro cell studies revealed that the PHA-TDVT hydrogel with the highest concentration of BMP-2 microspheres (i.e., PHA-TDVT+{micro}100) significantly improved calcium deposition and osteogenic gene expression. Minimal in vivo bone regeneration was observed for all hydrogel groups; however, BMP-2 microsphere addition fortuitously reduced motor skill impairment and brain atrophy. The PHA-TDVT+{micro}100 group had 2.8 times greater reach index and 2.3 times lower brain atrophy values compared to the negative control (p<0.05). Overall, hydrogels with controlled release of BMP-2 may provide neuroprotective benefits in TBI treatment. Future studies should explore BMP-2 delivery strategies to enhance both bone and brain recovery in rat TBI studies. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=82 SRC="FIGDIR/small/649206v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@136d4d4org.highwire.dtl.DTLVardef@cee564org.highwire.dtl.DTLVardef@13612e8org.highwire.dtl.DTLVardef@1134b4c_HPS_FORMAT_FIGEXP M_FIG C_FIG Statement of SignificanceSevere traumatic brain injury (TBI) is a life-threatening condition characterized by internal brain swelling and is commonly treated using a two-stage surgical approach. Complications associated with the two-stage treatment paradigm include secondary neurologic impairment, termed syndrome of the trephined (SOT). SOT is often reversible once the second surgery is performed, whereas a single-stage TBI treatment paradigm may avoid the occurrence of SOT altogether. Utilizing hydrogels comprised of pentenoate-modified hyaluronic acid and thiolated devitalized tendon encapsulating microspheres containing bone morphogenetic protein-2 (BMP-2), the current study demonstrated improvements in motor skill function and reductions in brain atrophy in a rat TBI model. The introduction of hydrogels with controlled release of BMP-2 as a neuroprotective strategy for TBI application offers a promising approach for single-stage TBI treatment.

bioengineering↗

bioRxiv2022

Mesoscale corticocortical connectivity corresponds with intracortical microstimulation-evoked neural activity

BackgroundCortical electrical stimulation has been a versatile technique for examining the structure and function of cortical regions as well as for implementing novel therapies. While electrical stimulation has been used to examine the local spread of neural activity, it may also enable longitudinal examination of mesoscale interregional connectivity. Recent studies have used focal intracortical microstimulation (ICMS) with optical imaging to show cross-region spread of neural activity, but techniques are limited to utilizing hemodynamic responses within anesthetized preparations. ObjectiveHere, we sought to use ICMS in conjunction with recordings of multi-unit action potentials to assess the mesoscale effective connectivity within sensorimotor cortex. MethodsNeural recordings were made from multielectrode arrays placed into sensory, motor, and premotor regions during surgical experiments in three squirrel monkeys. During each recording, single-pulse ICMS was repeatably delivered to a single region. Mesoscale effective connectivity was calculated from ICMS-evoked changes in multi-unit firing. ResultsMulti-unit action potentials were able to be detected on the order of 1 ms after each ICMS pulse. Across sensorimotor regions, short-latency (< 2.5 ms) ICMS-evoked neural activity strongly correlated with known anatomic connections. Additionally, ICMS-evoked responses remained stable across the experimental period, despite small changes in electrode locations and anesthetic state. ConclusionsThese results show that monitoring ICMS-evoked neural activity, in a technique we refer to as Stimulation-Evoked Effective Connectivity (SEEC), is a viable way to longitudinally assess effective connectivity enabling studies comparing the time course of connectivity changes with the time course of changes in behavioral function. HighlightsO_LIShort-latency neural responses to ICMS were evaluated in multiple cortical regions. C_LIO_LINeural responses strongly correlated with known anatomical connections. C_LIO_LIStimulation-evoked neural responses were maintained across repeated tests. C_LIO_LIICMS-evoked activity can show longitudinal changes in effective connectivity. C_LI

neuroscience↗

bioRxiv2020

Functional Suppression of Premotor Activity in a Transient Model of Motor Cortex Injury

Cortical injuries (e.g. - strokes or traumatic brain injuries) can create a host of secondary events that further impair the brains sensory, motor, or cognitive capabilities. Here, we attempted to isolate the acute effects of the primary injury - the loss of cortical activity - on rodent motor cortex (caudal forelimb area, CFA) without the secondary effects that arise from damage to cortical tissue. We then observed the effects of this loss of activity on the rodent premotor cortex (rostral forelimb area, RFA). In anesthetized rats, CFA was temporarily inactivated with the GABA-A agonist muscimol, disrupting motor network function while leaving neural connectivity intact. Using intracortical microstimulation (ICMS) techniques, we found that CFA inactivation completely abolished ICMS-evoked forelimb movement from RFA yet spared some CFA evoked-movement. Neural recordings confirmed that neural suppression by muscimol was isolated to CFA and did not spread into RFA. We next observed how CFA inactivation suppressed RFA influence on forelimb muscles by obtaining intramuscular electromyographical (EMG) recordings from forelimb muscles during ICMS. EMG recordings showed that despite the presence of evoked movement in CFA, but not RFA, muscle activation in both areas were similarly reduced. These results suggest that the primary reason for the loss of ICMS-evoked movement in RFA is not reduced forelimb muscle activity, but rather a loss of the specific activity between RFA and CFA. Therefore, within the intact motor network of the rat, RFAs influence on forelimb movement is mediated by CFA, similar to the premotor and motor organization observed in non-human primates.

neuroscience↗

bioRxiv2020

Anatomical Plasticity of the Distal Forelimb Projection of the Ventral Premotor Cortex Four weeks After Primary Motor Cortex Injury

Brain injury affecting the isocortical frontal cortex is a common pathological occurrence. Many patients report severe deficits to functions of daily living. However, there is a variable degree of motor recovery that occurs with some individuals recovering astounding degrees of motor recovery while others have not. This variability has led researchers into investigating the possible mechanisms for this variability. Recently, several non-human primate studies have shed light on the possibility of spared, ipsilesional motor area taken over the lost function to the damaged cortex. Unfortunately, these studies have focused on long-term adaption ranging from 5months to one year post injury. In this present study, we are the first use rigorous stereological quantification to show that significant neuroplastic changes in the form of changes to neuroanatomical connections between distant cortical area occurs at a very early time point of 4 weeks post injury. Much like the Dancause study in 2005, we found that ishemic damage to the distal forelimb area (DFL) of the primary motor cortex (M1) induced plastic changes between the DFL of the ventral premotor cortex (PMv) and area 1/2 of the somatosensory cortex. Indeed, we found a nearly 2 fold increase in the number of boutons between PMV and area 1/2. Additionally, labeled fibers from PMv change direction from their normal termination within M1 and traveled in a ventral posterior direction toward the somatosensory cortex. Also of interest, several labeled fibers actually traveled through the glial scar of M1 toward the somatosensory cortex. These data demonstrate that a massive neuroplastic response has occurred following an ischemic insult to the DFL of M1. These data may suggest that the brain may be undergoing an attempt to re-establish a degree of motor and or sensory control to compensate for the lost function due to the injury.

neuroscience↗

bioRxiv2020

Task Related Neural Activity Following Primary Motor Cortical Ischemic Injury in Rats

Acquired injuries to primary motor cortex (M1) contribute to motor impairment and disability. Functional recovery is predicated on the reorganization of spared areas, which has been demonstrated through cortical motor map representations and neuroanatomical projection and termination patterns. The purpose of this study was to understand how neurophysiological outputs of spared motor areas relate to motor recovery of a skilled reach task following an ischemic infarct to M1. We examined changes in single unit activity within ipsilesional pre-motor (PM) and contralesional M1 cortices of rats during a behavioral task after a unilateral ischemic injury to ipsilesional M1. The data show a shift in neuronal firing patterns in the contralateral PM and ipsilateral M1 during behavioral recovery in lesion rats compared to a non-lesion control group, suggesting that spike-timing properties are altered in specific phases of the task, and that this altered activity may support spontaneous restoration of motor behavior. SIGNIFICANCE STATEMENTFollowing ischemic stroke to primary motor cortex (M1), motor recovery is associated with reorganization of spared cortical motor areas in injured and spared hemispheres. Currently, it is unclear how cortical plasticity within spared motor areas relates to motor recovery. This study examines how task-related neural activity within spared motor areas in rats correlates with motor restoration of a skilled reach task following an ischemic infarct to M1. The data suggest contralateral pre-motor and ipsilateral M1 alter their neural response profiles with respect to the timing of a motor task during recovery. To our knowledge, this is the first demonstration of a compensatory single-spike neurophysiological mechanism that may explain how remote, spared cortical areas contribute to functional recovery after M1 injury.

neuroscience↗

bioRxiv2020

Corticocortical Connections of the Rostral Forelimb Area in Rats: A Quantitative Tract-Tracing Study

The rostral forelimb area (RFA) in the rat is considered to be a premotor cortical region based primarily on its efferent projections to the primary motor cortex. The purpose of the present study was to identify corticocortical connections of RFA, and to describe the relative strength of connections with other cortical areas. This will allow us to better understand the broader cortical network in which RFA participates, and thus, determine its function in motor behavior. In the present study, the RFA of adult male Long-Evans rats (n=6) was identified using intracortical microstimulation techniques and injected with the tract tracer, biotinylated dextran amine (BDA). In post-mortem tissue, location of BDA-labeled terminal boutons and neuronal somata were plotted and superimposed on cortical field boundaries. The results demonstrated that the RFA has dense to moderate reciprocal connections with primary motor cortex, the frontal cortex medial and lateral to RFA, primary somatosensory cortex (S1), and lateral somatosensory areas. Importantly, S1 connections were dense to moderate in dysgranular zones, but sparse to negligible in granular zones. Cortical connections of RFA in rat are strikingly similar to cortical connections of the ventral premotor cortex in non-human primates, suggesting that these areas share similar functions.

neuroscience↗