Neeraj Jain

Bio: Neeraj Jain is an academic researcher from National Brain Research Centre. The author has contributed to research in topics: Somatosensory system & Cortex (anatomy). The author has an hindex of 26, co-authored 51 publications receiving 2271 citations. Previous affiliations of Neeraj Jain include Indian Institute of Technology, Jodhpur & University of Maryland, Baltimore.

RNA-mediated immunotherapy regulating tumor immune microenvironment: next wave of cancer therapeutics

Abstract: Accumulating research suggests that the tumor immune microenvironment (TIME) plays an essential role in regulation of tumor growth and metastasis. The cellular and molecular nature of the TIME influences cancer progression and metastasis by altering the ratio of immune- suppressive versus cytotoxic responses in the vicinity of the tumor. Targeting or activating the TIME components show a promising therapeutic avenue to combat cancer. The success of immunotherapy is both astounding and unsatisfactory in the clinic. Advancements in RNA-based technology have improved understanding of the complexity and diversity of the TIME and its effects on therapy. TIME-related RNA or RNA regulators could be promising targets for anticancer immunotherapy. In this review, we discuss the available RNA-based cancer immunotherapies targeting the TIME. More importantly, we summarize the potential of various RNA-based therapeutics clinically available for cancer treatment. RNA-dependent targeting of the TIME, as monotherapy or combined with other evolving therapeutics, might be beneficial for cancer patients' treatment in the near future.

Large-scale reorganization of the somatosensory cortex of adult macaque monkeys revealed by fMRI

Abstract: Somatosensory cortex of adult primates undergoes topographic reorganization following spinal cord or peripheral nerve injuries. Electrophysiological studies in monkeys show that after chronic lesions of dorsal columns of the spinal cord at cervical levels, there is an expansion of face representation into the deafferented hand region of area 3b of cortex. However, these techniques can sample only a limited portion of the brain. In order to help understand mechanisms of brain reorganization use of noninvasive tools in non-human primate experimental model is important. Use of blood oxygen level dependent-functional magnetic resonance imaging (BOLD-fMRI) to study brain reorganization in non-human primates has been extremely limited. Here, we show that in monkeys with long-term unilateral lesions of the dorsal columns at cervical levels, tactile stimulation of the chin showed BOLD activation in the deafferented hand region of contralesional area 3b in the post-central gyrus. In a monkey with a partial lesion of the dorsal columns, stimulations of both hand and chin activated the partially deafferented hand region. We also show that the somatotopic organization in the non-deafferented ipsilesional somatosensory cortex remained normal.

Complete reorganization of the motor cortex of adult rats following long-term spinal cord injuries.

Abstract: Understanding brain reorganization following long-term spinal cord injuries is important for optimizing recoveries based on residual function as well as developing brain-controlled assistive devices. Although it has been shown that the motor cortex undergoes partial reorganization within a few weeks after peripheral and spinal cord injuries, it is not known if the motor cortex of rats is capable of large-scale reorganization after longer recovery periods. Here we determined the organization of the rat (Rattus norvegicus) motor cortex at 5 or more months after chronic lesions of the spinal cord at cervical levels using intracortical microstimulation. The results show that, in the rats with the lesions, stimulation of neurons in the de-efferented forelimb motor cortex no longer evokes movements of the forelimb. Instead, movements of the body parts in the adjacent representations, namely the whiskers and neck were evoked. In addition, at many sites, movements of the ipsilateral forelimb were observed at threshold currents. The extent of representations of the eye, jaw and tongue movements was unaltered by the lesion. Thus, large-scale reorganization of the motor cortex leads to complete filling-in of the de-efferented cortex by neighboring representations following long-term partial spinal cord injuries at cervical levels in adult rats.

Ipsilateral cortical inputs to the rostral and caudal motor areas in rats.

Abstract: Rats have a complete body representation in the primary motor cortex (M1). Rostrally there are additional representations of the forelimb and whiskers, called the rostral forelimb area (RFA) and the rostral whisker area (RWA). Recently we showed that sources of thalamic inputs to RFA and RWA are similar, but they are different from those for the caudal forelimb area (CFA) and the caudal whisker area (CWA) of M1 (Mohammed and Jain [2014] J Comp Neurol 522:528-545). We proposed that RWA and RFA are part of a second motor area, the rostral motor area (RMA). Here we report ipsilateral cortical connections of whisker representation in RMA, and compare them with connections of CWA. Connections of RFA, CFA, and the caudally located hindlimb area (CHA), which is a part of M1, were determined for comparison. The most distinctive features of cortical inputs to RWA compared with CWA include lack of inputs from the face region of the primary somatosensory cortex (S1), and only about half as much inputs from S1 compared with the lateral somatosensory areas S2 (second somatosensory area) and the parietal ventral area (PV). A similar pattern of inputs is seen for CFA and RFA, with RFA receiving smaller proportion of inputs from the forepaw region of S1 compared with CFA, and receiving fewer inputs from S1 compared with those from S2. These and other features of the cortical input pattern suggest that RMA has a distinct, and more of integrative functional role compared with M1. J. Comp. Neurol. 524:3104-3123, 2016. © 2016 Wiley Periodicals, Inc.

Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models.

Abstract: Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans.

Treatment-Induced Cortical Reorganization After Stroke in Humans

Abstract: Background and Purpose—Injury-induced cortical reorganization is a widely recognized phenomenon. In contrast, there is almost no information on treatment-induced plastic changes in the human brain. The aim of the present study was to evaluate reorganization in the motor cortex of stroke patients that was induced with an efficacious rehabilitation treatment. Methods—We used focal transcranial magnetic stimulation to map the cortical motor output area of a hand muscle on both sides in 13 stroke patients in the chronic stage of their illness before and after a 12-day-period of constraint-induced movement therapy. Results—Before treatment, the cortical representation area of the affected hand muscle was significantly smaller than the contralateral side. After treatment, the muscle output area size in the affected hemisphere was significantly enlarged, corresponding to a greatly improved motor performance of the paretic limb. Shifts of the center of the output map in the affected hemisphere suggested the recru...

Plasticity and primary motor cortex.

Abstract: One fundamental function of primary motor cortex (MI) is to control voluntary movements. Recent evidence suggests that this role emerges from distributed networks rather than discrete representations and that in adult mammals these networks are capable of modification. Neuronal recordings and activation patterns revealed with neuroimaging methods have shown considerable plasticity of MI representations and cell properties following pathological or traumatic changes and in relation to everyday experience, including motor-skill learning and cognitive motor actions. The intrinsic horizontal neuronal connections in MI are a strong candidate substrate for map reorganization: They interconnect large regions of MI, they show activity-dependent plasticity, and they modify in association with skill learning. These findings suggest that MI cortex is not simply a static motor control structure. It also contains a dynamic substrate that participates in motor learning and possibly in cognitive events as well.

The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats.

Abstract: In contrast to peripheral nerves, central axons do not regenerate. Partial injuries to the spinal cord, however, are followed by functional recovery. We investigated the anatomical basis of this recovery and found that after incomplete spinal cord injury in rats, transected hindlimb corticospinal tract (CST) axons sprouted into the cervical gray matter to contact short and long propriospinal neurons (PSNs). Over 12 weeks, contacts with long PSNs that bridged the lesion were maintained, whereas contacts with short PSNs that did not bridge the lesion were lost. In turn, long PSNs arborize on lumbar motor neurons, creating a new intraspinal circuit relaying cortical input to its original spinal targets. We confirmed the functionality of this circuit by electrophysiological and behavioral testing before and after CST re-lesion. Retrograde transynaptic tracing confirmed its integrity, and revealed changes of cortical representation. Hence, after incomplete spinal cord injury, spontaneous extensive remodeling occurs, based on axonal sprout formation and removal. Such remodeling may be crucial for rehabilitation in humans.