Stimulating the nervous system and measuring muscle response offers a unique opportunity to inter... more Stimulating the nervous system and measuring muscle response offers a unique opportunity to interrogate motor system function. Often, this is performed by stimulating motor cortex and recording muscle activity with electromyography; the evoked response is called the motor evoked potential (MEP). To understand system dynamics, MEPs are typically recorded through a range of motor cortex stimulation intensities. The MEPs increase with increasing stimulation intensities, and these typically produce a sigmoidal response curve. Analysis of MEPs is often complex and analysis of response curves is time-consuming. We created an MEP analysis software, called Motometrics, to facilitate analysis of MEPs and response curves. The goal is to combine robust signal processing algorithms with a simple user interface. Motometrics first enables the user to annotate data files acquired from the recording system so that the responses can be extracted and labeled with the correct subject and experimental condition. The software enables quick visual representations of entire datasets, to ensure uniform quality of the signal. It then enables the user to choose a variety of response curve analyses and to perform near real time quantification of the MEPs for quick feedback during experimental procedures. This is a modular open source tool that is compatible with several popular electrophysiological systems. Initial use indicates that Motometrics enables rapid, robust, and intuitive analysis of MEP response curves by neuroscientists without programming or signal processing expertise.
Autism spectrum disorder (ASD) is a heterogeneous category of developmental psychiatric disorders... more Autism spectrum disorder (ASD) is a heterogeneous category of developmental psychiatric disorders which is characterized by inadequate social interaction, less communication, and repetitive phenotype behavior. ASD is comorbid with various types of disorders. The reported prevalence is 1% in the United Kingdom, 1.5% in the United States, and ~0.2% in India at present. The natural anti-inflammatory agents on brain development are linked to interaction with many types of inflammatory pathways affected by genetic, epigenetic, and environmental variables. Inflammatory targeting pathways have already been linked to ASD. However, these routes are diluted, and new strategies are being developed in natural anti-inflammatory medicines to treat ASD. This review summarizes the numerous preclinical and clinical studies having potential protective effects and natural anti-inflammatory agents on the developing brain during pregnancy. Inflammation during pregnancy activates the maternal infection t...
Traumatic spinal cord injury (SCI) is one of the most incapacitating pathologies, leading to huge... more Traumatic spinal cord injury (SCI) is one of the most incapacitating pathologies, leading to huge rehabilitation challenges besides a social-economic burden on SCI patients and their families. There is no complete curative treatment available so far. Non-invasive and patient-friendly use of extremely low-frequency electromagnetic field stimulation (EMF) has emerged as a therapeutic and rehabilitation option. In this study, we tested whole-body EMF stimulation on thoracic complete SCI-induced nociception including sensorimotor deficits in rats. The EMF application significantly attenuated hyperalgesia and allodynia to thermal, electrical, and chemical stimuli from 6 weeks onwards as well as restoration of spinal reflexes, viz., H-reflex and nociceptive flexion reflex at the study endpoint (week 8). Besides, massively increased glutamate at the SCI injury site was observed in SCI rats with no treatment, which was also attenuated significantly by EMF stimulation. Spinal cord histology ...
The present study aimed to evaluate the effect of iron oxide nanoparticles (IONPs) along with ele... more The present study aimed to evaluate the effect of iron oxide nanoparticles (IONPs) along with electromagnetic fields (MF) exposure on spontaneous and induced axonal sprouting after spinal cord injury (SCI). Adult male Wistar rats were subjected to spinal cord transection at the T13 segment. The IONP (25 μg/mL) embedded in 3% agarose gel was implanted at the injury site and subsequently exposed to MF (50 Hz, 17.96 μT, 2 hours/day for 5 weeks). Histological analysis of spinal cord tissue showed a significant increase in the expression of the growth-associated protein GAP-43 and it was found to be co-localized with neuronal nuclei marker and neurofilaments. The results show sprouting from mature neurons and axons, significantly less demyelination and more myelinated fibers were evident at the lesion site. However, no motor or somatosensory evoked potential response was observed, suggesting lack of long-distance functional connectivity. These findings highlight the therapeutic potential...
We sought to develop a cervical spinal cord stimulator for the rat that is durable, stable, and d... more We sought to develop a cervical spinal cord stimulator for the rat that is durable, stable, and does not perturb the underlying spinal cord. We created a softening spinal cord stimulation (SCS) array made from shape memory polymer (SMP)-based flexible electronics. We developed a new photolithographic process to pattern high surface area titanium nitride (TiN) electrodes onto gold (Au) interconnects. The thiol-ene acrylate polymers are stiff at room temperature and soften following implantation into the body. Durability was measured by the duration the devices produced effective stimulation and by accelerated aging in vitro. Stability was measured by the threshold to provoke an electromyogram (EMG) muscle response and by measuring impedance using electrochemical impedance spectroscopy (EIS). In addition, spinal cord modulation of motor cortex potentials was measured. The spinal column and implanted arrays were imaged with MRI ex vivo, and histology for astrogliosis and immune reactio...
Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation... more Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord. r The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone. r Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal. r Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord.
ABSTRACT Electromagnetic field (EMF) stimulation improves the microenvironment for the nerve rege... more ABSTRACT Electromagnetic field (EMF) stimulation improves the microenvironment for the nerve regeneration by stimulating neurotrophic factor release, attenuating oxidative stress and apoptosis after injury. Iron oxide nanoparticles (IONPs) in combination with an external electromagnetic field can also facilitate axon regeneration invitro. The present study demonstrates the in vivo potential of EMF and IONPs to facilitate regeneration in rats with complete spinal cord injury. The spinal cord was completely transected at the T11 vertebra in male albino Wistar rats. The injured rats were exposed to EMF after 24h of surgery daily for five weeks (50 Hz, 17.96 μT for two hours). In a separate group of injured rats, iron oxide nanoparticle solution (25 μg/mL) embedded in 3% agarose gel was implanted at the site of transaction and the rats subsequently exposed to EMF. BBB score was done weekly to assess locomotion and for neuroregeneration, expression of growth associated protein (GAP-43) was observed. Locomotor assessment as well as histological analysis by cresyl-violet staining demonstrated significant functional recovery and a reduction in lesion volume in rats with IONP implantation and EMF exposure. Immunohistological analysis of spinal cord tissue for GAP-43 in these rats showed a significant (P<0.001) increase in the expression and it was found to be colocalized with NeuN and NF160 as compared to SCI only group of rats. Confocal images showed abundant sprouting from mature neurons and axons near the site of lesion. Area of demyelination was also significantly less and myelinated fibers were evident at the lesion site. However, no significant difference in the expression of GFAP was evident. These findings highlight the possible therapeutic potential of IONPs along with EMF exposure in promoting neuroregeneration after SCI.
Iron oxide nanoparticles (IONPs) can attenuate oxidative stress in a neutral pH environment in vi... more Iron oxide nanoparticles (IONPs) can attenuate oxidative stress in a neutral pH environment in vitro. In combination with an external electromagnetic field, they can also facilitate axon regeneration. The present study demonstrates the in vivo potential of IONPs to recover functional deficits in rats with complete spinal cord injury. Methods: The spinal cord was completely transected at the T11 vertebra in male albino Wistar rats. Iron oxide nanoparticle solution (25 µg/mL) embedded in 3% agarose gel was implanted at the site of transection, which was subsequently exposed to an electromagnetic field (50 Hz, 17.96 µT for two hours daily for five weeks). Results: Locomotor and sensorimotor assessment as well as histological analysis demonstrated significant functional recovery and a reduction in lesion volume in rats with IONP implantation and exposure to an electromagnetic field. No collagenous scar was observed and IONPs were localized intracellularly in the immediate vicinity of the lesion. Further, in vitro experiments to explore the cytotoxic effects of IONPs showed no effect on cell survival. However, a significant decrease in H 2 O 2 -mediated oxidative stress was evident in the medium containing IONPs, indicating their free radical scavenging properties. Conclusion: These novel findings indicate a therapeutic role for IONPs in spinal cord injury and other neurodegenerative disorders mediated by reactive oxygen species.
Associative plasticity occurs when two stimuli converge on a common neural target. Previous effor... more Associative plasticity occurs when two stimuli converge on a common neural target. Previous efforts to promote associative plasticity have targeted cortex, with variable and moderate effects. In addition, the targeted circuits are inferred, rather than tested directly. In contrast, we sought to target the strong convergence between motor and sensory systems in the spinal cord.We developed spinal cord associative plasticity (SCAP), precisely timed pairing of motor cortex and dorsal spinal cord stimulations, to target this interaction. We tested the hypothesis that properly timed paired stimulation would strengthen the sensorimotor connections in the spinal cord and improve recovery after spinal cord injury (SCI). We tested physiological effects of paired stimulation, the pathways that mediate it, and its function in a preclinical trial.Subthreshold spinal cord stimulation strongly augmented motor cortex evoked muscle potentials at the time they were paired, but only when they arrived...
Stimulating the nervous system and measuring muscle response offers a unique opportunity to inter... more Stimulating the nervous system and measuring muscle response offers a unique opportunity to interrogate motor system function. Often, this is performed by stimulating motor cortex and recording muscle activity with electromyography; the evoked response is called the motor evoked potential (MEP). To understand system dynamics, MEPs are typically recorded through a range of motor cortex stimulation intensities. The MEPs increase with increasing stimulation intensities, and these typically produce a sigmoidal response curve. Analysis of MEPs is often complex and analysis of response curves is time-consuming. We created an MEP analysis software, called Motometrics, to facilitate analysis of MEPs and response curves. The goal is to combine robust signal processing algorithms with a simple user interface. Motometrics first enables the user to annotate data files acquired from the recording system so that the responses can be extracted and labeled with the correct subject and experimental condition. The software enables quick visual representations of entire datasets, to ensure uniform quality of the signal. It then enables the user to choose a variety of response curve analyses and to perform near real time quantification of the MEPs for quick feedback during experimental procedures. This is a modular open source tool that is compatible with several popular electrophysiological systems. Initial use indicates that Motometrics enables rapid, robust, and intuitive analysis of MEP response curves by neuroscientists without programming or signal processing expertise.
Autism spectrum disorder (ASD) is a heterogeneous category of developmental psychiatric disorders... more Autism spectrum disorder (ASD) is a heterogeneous category of developmental psychiatric disorders which is characterized by inadequate social interaction, less communication, and repetitive phenotype behavior. ASD is comorbid with various types of disorders. The reported prevalence is 1% in the United Kingdom, 1.5% in the United States, and ~0.2% in India at present. The natural anti-inflammatory agents on brain development are linked to interaction with many types of inflammatory pathways affected by genetic, epigenetic, and environmental variables. Inflammatory targeting pathways have already been linked to ASD. However, these routes are diluted, and new strategies are being developed in natural anti-inflammatory medicines to treat ASD. This review summarizes the numerous preclinical and clinical studies having potential protective effects and natural anti-inflammatory agents on the developing brain during pregnancy. Inflammation during pregnancy activates the maternal infection t...
Traumatic spinal cord injury (SCI) is one of the most incapacitating pathologies, leading to huge... more Traumatic spinal cord injury (SCI) is one of the most incapacitating pathologies, leading to huge rehabilitation challenges besides a social-economic burden on SCI patients and their families. There is no complete curative treatment available so far. Non-invasive and patient-friendly use of extremely low-frequency electromagnetic field stimulation (EMF) has emerged as a therapeutic and rehabilitation option. In this study, we tested whole-body EMF stimulation on thoracic complete SCI-induced nociception including sensorimotor deficits in rats. The EMF application significantly attenuated hyperalgesia and allodynia to thermal, electrical, and chemical stimuli from 6 weeks onwards as well as restoration of spinal reflexes, viz., H-reflex and nociceptive flexion reflex at the study endpoint (week 8). Besides, massively increased glutamate at the SCI injury site was observed in SCI rats with no treatment, which was also attenuated significantly by EMF stimulation. Spinal cord histology ...
The present study aimed to evaluate the effect of iron oxide nanoparticles (IONPs) along with ele... more The present study aimed to evaluate the effect of iron oxide nanoparticles (IONPs) along with electromagnetic fields (MF) exposure on spontaneous and induced axonal sprouting after spinal cord injury (SCI). Adult male Wistar rats were subjected to spinal cord transection at the T13 segment. The IONP (25 μg/mL) embedded in 3% agarose gel was implanted at the injury site and subsequently exposed to MF (50 Hz, 17.96 μT, 2 hours/day for 5 weeks). Histological analysis of spinal cord tissue showed a significant increase in the expression of the growth-associated protein GAP-43 and it was found to be co-localized with neuronal nuclei marker and neurofilaments. The results show sprouting from mature neurons and axons, significantly less demyelination and more myelinated fibers were evident at the lesion site. However, no motor or somatosensory evoked potential response was observed, suggesting lack of long-distance functional connectivity. These findings highlight the therapeutic potential...
We sought to develop a cervical spinal cord stimulator for the rat that is durable, stable, and d... more We sought to develop a cervical spinal cord stimulator for the rat that is durable, stable, and does not perturb the underlying spinal cord. We created a softening spinal cord stimulation (SCS) array made from shape memory polymer (SMP)-based flexible electronics. We developed a new photolithographic process to pattern high surface area titanium nitride (TiN) electrodes onto gold (Au) interconnects. The thiol-ene acrylate polymers are stiff at room temperature and soften following implantation into the body. Durability was measured by the duration the devices produced effective stimulation and by accelerated aging in vitro. Stability was measured by the threshold to provoke an electromyogram (EMG) muscle response and by measuring impedance using electrochemical impedance spectroscopy (EIS). In addition, spinal cord modulation of motor cortex potentials was measured. The spinal column and implanted arrays were imaged with MRI ex vivo, and histology for astrogliosis and immune reactio...
Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation... more Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord. r The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone. r Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal. r Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord.
ABSTRACT Electromagnetic field (EMF) stimulation improves the microenvironment for the nerve rege... more ABSTRACT Electromagnetic field (EMF) stimulation improves the microenvironment for the nerve regeneration by stimulating neurotrophic factor release, attenuating oxidative stress and apoptosis after injury. Iron oxide nanoparticles (IONPs) in combination with an external electromagnetic field can also facilitate axon regeneration invitro. The present study demonstrates the in vivo potential of EMF and IONPs to facilitate regeneration in rats with complete spinal cord injury. The spinal cord was completely transected at the T11 vertebra in male albino Wistar rats. The injured rats were exposed to EMF after 24h of surgery daily for five weeks (50 Hz, 17.96 μT for two hours). In a separate group of injured rats, iron oxide nanoparticle solution (25 μg/mL) embedded in 3% agarose gel was implanted at the site of transaction and the rats subsequently exposed to EMF. BBB score was done weekly to assess locomotion and for neuroregeneration, expression of growth associated protein (GAP-43) was observed. Locomotor assessment as well as histological analysis by cresyl-violet staining demonstrated significant functional recovery and a reduction in lesion volume in rats with IONP implantation and EMF exposure. Immunohistological analysis of spinal cord tissue for GAP-43 in these rats showed a significant (P<0.001) increase in the expression and it was found to be colocalized with NeuN and NF160 as compared to SCI only group of rats. Confocal images showed abundant sprouting from mature neurons and axons near the site of lesion. Area of demyelination was also significantly less and myelinated fibers were evident at the lesion site. However, no significant difference in the expression of GFAP was evident. These findings highlight the possible therapeutic potential of IONPs along with EMF exposure in promoting neuroregeneration after SCI.
Iron oxide nanoparticles (IONPs) can attenuate oxidative stress in a neutral pH environment in vi... more Iron oxide nanoparticles (IONPs) can attenuate oxidative stress in a neutral pH environment in vitro. In combination with an external electromagnetic field, they can also facilitate axon regeneration. The present study demonstrates the in vivo potential of IONPs to recover functional deficits in rats with complete spinal cord injury. Methods: The spinal cord was completely transected at the T11 vertebra in male albino Wistar rats. Iron oxide nanoparticle solution (25 µg/mL) embedded in 3% agarose gel was implanted at the site of transection, which was subsequently exposed to an electromagnetic field (50 Hz, 17.96 µT for two hours daily for five weeks). Results: Locomotor and sensorimotor assessment as well as histological analysis demonstrated significant functional recovery and a reduction in lesion volume in rats with IONP implantation and exposure to an electromagnetic field. No collagenous scar was observed and IONPs were localized intracellularly in the immediate vicinity of the lesion. Further, in vitro experiments to explore the cytotoxic effects of IONPs showed no effect on cell survival. However, a significant decrease in H 2 O 2 -mediated oxidative stress was evident in the medium containing IONPs, indicating their free radical scavenging properties. Conclusion: These novel findings indicate a therapeutic role for IONPs in spinal cord injury and other neurodegenerative disorders mediated by reactive oxygen species.
Associative plasticity occurs when two stimuli converge on a common neural target. Previous effor... more Associative plasticity occurs when two stimuli converge on a common neural target. Previous efforts to promote associative plasticity have targeted cortex, with variable and moderate effects. In addition, the targeted circuits are inferred, rather than tested directly. In contrast, we sought to target the strong convergence between motor and sensory systems in the spinal cord.We developed spinal cord associative plasticity (SCAP), precisely timed pairing of motor cortex and dorsal spinal cord stimulations, to target this interaction. We tested the hypothesis that properly timed paired stimulation would strengthen the sensorimotor connections in the spinal cord and improve recovery after spinal cord injury (SCI). We tested physiological effects of paired stimulation, the pathways that mediate it, and its function in a preclinical trial.Subthreshold spinal cord stimulation strongly augmented motor cortex evoked muscle potentials at the time they were paired, but only when they arrived...
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