Hari Sharma

Uppsala University | UU · Department of Surgical Sciences

Curcumin is a well-known antioxidant used as traditional medicine in China and India since ages to treat variety of inflammatory ailments as a food supplement. Curcumin has antitumor properties with neuroprotective effects in Alzheimer's disease. Curcumin elevates brain-derived neurotrophic factor (BDNF) and dopamine (DA) levels in the brain indica...

Blast brain injury (bBI) following explosive detonations in warfare is one of the prominent causes of multidimensional insults to the central nervous and other vital organs injury. Several military personnel suffered from bBI during the Middle East conflict at hot environment. The bBI largely occurs due to pressure waves, generation of heat togethe...

dl-3-n-butylphthalide (dl-NBP) is one of the potent antioxidant compounds that induces profound neuroprotection in stroke and traumatic brain injury. Our previous studies show that dl-NBP reduces brain pathology in Parkinson's disease (PD) following its nanowired delivery together with mesenchymal stem cells (MSCs) exacerbated by concussive head in...

Military personnel are often exposed to silica dust during combat operations across the globe. Exposure to silica dust in US military or service personnel could cause Desert Strom Pneumonitis also referred to as Al Eskan disease causing several organs damage and precipitate autoimmune dysfunction. However, the effects of microfine particles of sand...

Sleep deprivation induces amyloid beta peptide and phosphorylated tau deposits in the brain and cerebrospinal fluid together with altered serotonin metabolism. Thus, it is likely that sleep deprivation is one of the predisposing factors in precipitating Alzheimer's disease (AD) brain pathology. Our previous studies indicate significant brain pathol...

Parkinson's disease (PD) in military personnel engaged in combat operations is likely to develop in their later lives. In order to enhance the quality of lives of PD patients, exploration of novel therapy based on new research strategies is highly warranted. The hallmarks of PD include increased alpha synuclein (ASNC) and phosphorylated tau (p-tau)...

Military personnel are often exposed to hot environments either for combat operations or peacekeeping missions. Hot environment is a severe stressful situation leading to profound hyperthermia, fatigue and neurological impairments. To avoid stressful environment, some people frequently use methamphetamine (METH) or other psychostimulants to feel co...

Environmental temperature adversely affects the outcome of concussive head injury (CHI)-induced brain pathology. Studies from our laboratory showed that animals reared at either cold environment or at hot environment exacerbate brain pathology following CHI. Our previous experiments showed that nanowired delivery of oxiracetam significantly attenua...

Concussive head injury (CHI) is one of the major risk factors in developing Alzheimer's disease (AD) in military personnel at later stages of life. Breakdown of the blood-brain barrier (BBB) in CHI leads to extravasation of plasma amyloid beta protein (ΑβP) into the brain fluid compartments precipitating AD brain pathology. Oxidative stress in CHI...

Military personnel during combat or peacekeeping operations are exposed to extreme climates of hot or cold environments for longer durations. Spinal cord injury is quite common in military personnel following central nervous system (CNS) trauma indicating a possibility of altered pathophysiological responses at different ambient temperatures. Our p...

Neuropathic pain is associated with abnormal sensations and/or pain induced by non-painful stimuli, i.e., allodynia causing burning or cold sensation, pinching of pins and needles like feeling, numbness, aching or itching. However, no suitable therapy exists to treat these pain syndromes. Our laboratory explored novel potential therapeutic strategi...

Depression caused by either genetic factors or environmental stimulates such as chronic psychological or physiological stress, traumatic or sports-related brain injuries, neurodegenerative diseases, and/or substance abuse and drug dependence leads to serious neurological manifestation and affects mortality and morbidity since ages. Stress is one of...

Breakthroughs with rapid changes are the themes of the development in Neurorestoratology this year. Given the very difficult circumstances of the persistent COVID-19 pandemic, most of the colleagues in Neurorestoratology have conducted meaningful research and obtained encouraging results, as described in the 2020 Yearbook of Neurorestoratology. Neu...

Neurorestorative treatments have been able to improve the quality of life for patients suffering from neurological diseases and damages since the concept of Neurorestoratology was proposed. The discipline of Neurorestoratology focuses to restore impaired neurological functions and/or structures through the varying neurorestorative mechanisms includ...

The scales evaluating patients’ neurological functions and quality of life are the basis of clinical evaluation and/or scientific research of nervous system diseases. Neurological functions of patients with spinal cord injury (SCI) are commonly assessed by using American Spinal Injury Association (ASIA) Impairment Scale or International Standards f...

Cell therapy has been shown to be a crucial clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is essential for promoting professional associations devoted to cell therapy. The International Association of Neurorestoratology (IANR) and the Chinese Association of Neurorestor...

Military personnel are prone to traumatic brain injury (TBI) that is one of the risk factors in developing Alzheimer's disease (AD) at a later stage. TBI induces breakdown of the blood-brain barrier (BBB) to serum proteins into the brain and leads to extravasation of plasma amyloid beta peptide (ΑβP) into the brain fluid compartments causing AD bra...

Military personnel are the most susceptible to concussive head injury (CHI) caused by explosion, blast or missile or blunt head trauma. Mild to moderate CHI could induce lifetime functional and cognitive disturbances causing significant decrease in quality of life. Severe CHI leads to instant death and lifetime paralysis. Thus, further exploration...

Glioblastoma (GBM) is the most common and the most aggressive primary malignant brain tumor in adults. Although tumor recurrence is inevitable, leptomeningeal spread is relatively rare. We describe a case of leptomeningeal spread recurrent GBM treated with anlotinib in this report. When the recurrent GBM patient had leptomeningeal spread was admini...

Oxidative stress plays an important role in neuronal injuries after cardiac arrest. Increased production of carbon monoxide (CO) by the enzyme hemeoxygenase (HO) in the brain is induced by the oxidative stress. HO is present in the CNS in two isoforms, namely the inducible HO-1 and the constitutive HO-2. Elevated levels of serum HO-1 occurs in card...

Nanoparticles affect blood-brain barrier (BBB) and brain edema formation resulting in sensory-motor dysfunction. Exposure of Mn nanoparticles from industrial sources in humans could target basal ganglia resulting in Parkinson's disease. In present investigation, Mn exposure on brain pathology in a rat model was examined. Rats received Mn nanopartic...

Objective: Cinobufotalin was extracted from the skin of Chinese giant salamander or black sable with good clinical effect against tumor. This study aims to explore the mechanism of Cinobufotalin components and predict the target of action of Cinobufotalin on glioma. Methods: The active components of Cinobufotalin were screened by the Chinese med...

Military personnel often exposed to high summer heat are vulnerable to heat stroke (HS) resulting in abnormal brain function and mental anomalies. There are reasons to believe that leakage of the blood-brain barrier (BBB) due to hyperthermia and development of brain edema could result in brain pathology. Thus, exploration of suitable therapeutic st...

Clinical neurorestorative cell therapies for stroke have been explored for over 20 years. Majority cell therapies have shown neurorestorative effects for stroke on non-double-blind studies. In this review, we summarize types of cell transplantation, transplanted routes, therapeutic time windows, dosage, results of exploring trials or clinical studi...

Background: Glioma is the most common malignant primary brain tumor and it will always recur. To date, various multimodal imaging including magnetic resonance imaging (MRI) and positron emission tomography computed tomography (PET/CT) was used to differentiate the diagnosis of true tumor recurrent (TuR) and treatment-related effects (TrE) in gliom...

Glioblastoma multiforme (GBM) is an extremely aggressive primary human brain tumor. The median survival of GBM patients is 15 months in case of completing the modern complex treatment protocol. Chemotherapy can help to extend the life expectancy of patients. GBM treatment resistance is associated with cancer stem cells (CSCs). The present paper ana...

Objective: This study discusses the therapeutic effect of high-dose urokinase treatment for hypertension ventricular hemorrhage. Methods: A total of 60 patients with hypertension ventricular hemorrhage were randomly assigned to two groups: treatment group (n=30) and control group (n=30). Both groups received bilateral external ventricular drain....

Background: Glioblastoma multiforme (GBM) is a primary human brain tumor with the highest mortality rate. The prognosis for such patients is unfavorable, since the tumor is highly resistant to treatment, and the median survival of patients is 13 months. Chemotherapy might extend patients' life, but a tumor, that reappears after chemoradiotherapy, i...

Military personnel deployed in combat operations are highly prone to develop Parkinson's disease (PD) in later lives. PD largely involves dopaminergic pathways with hallmarks of increased alpha synuclein (ASNC), and phosphorylated tau (p-tau) in the cerebrospinal fluid (CSF) precipitating brain pathology. However, increased histaminergic nerve fibe...

Background: The incidence of cervical, thoracic and lumbar spinal canal stenosis is low. It is difficult to identify the main focus and responsible segment, and it is also difficult to select the sequence of staging surgery. We report a patient with triple stenosis. Case presentation: In this paper, we introduced a 61-year-old female patient with c...

The comparative study of the protein markers of the membrane surface of the autologous hematopoietic stem cells (СD34 + СD45 +) was performed to detect the patterns of the proteomic profiles, if any. The study included five groups. The subpopulations of the hematopoietic stem cells were studied in 569 samples of the mobilized peripheral blood monon...

Military personnel are often exposed to high altitude (HA, ca. 4500–5000 m) for combat operations associated with neurological dysfunctions. HA is a severe stressful situation and people frequently use methamphetamine (METH) or other psychostimulants to cope stress. Since military personnel are prone to different kinds of traumatic brain injury (TB...

Concussive head injury (CHI) often associated with military personnel, soccer players and related sports personnel leads to serious clinical situation causing lifetime disabilities. About 3–4 k head injury per 100 k populations are recorded in the United States since 2000–2014. The annual incidence of concussion has now reached to 1.2% of populatio...

Military personnel are often exposed to high environmental heat associated with industrial or ambient abundance of nanoparticles (NPs) affecting brain function. We have shown that engineered metal NPs Ag and Cu exacerbate hyperthermia induced brain pathology. Thus, exploration of novel drug therapy is needed for effective neuroprotection in heat st...

Spinal cord injury (SCI) is one of the most challenging medical issues. Spasticity is a major complication of SCI. A combination of spinal cord stimulation, new methods of neuroprotection and biomedical cellular products provides fundamentally new options for SCI treatment and rehabilitation. The paper attempts to critically analyze the effectivene...

Military personnel are vulnerable to environmental or industrial exposure of engineered nanoparticles (NPs) from metals. Long-term exposure of NPs from various sources affect sensory-motor or cognitive brain functions. Thus, a possibility exists that chronic exposure of NPs affect blood-brain barrier (BBB) breakdown and brain pathology by inducing...

Spinal cord injury (SCI) is one of the leading causes of disability in Military personnel for which no suitable therapeutic strategies are available till today. Thus, exploration of novel therapeutic measures is highly needed to enhance the quality of life of SCI victims. Previously, topical application of BDNF and GDNF in combination over the inju...

Glioblastoma multiforme (GBM) is one of the most aggressive types of brain tumor in humans. The prognosis for patients with GBM is unfavorable and treatment is largely ineffective, where modern treatment regimens typically increase survival by 15 months. GBM relapse and progression are associated with cancer stem cells (CSCs). The present review pr...

Glioblastoma multiforme (GBM) is the most common primary tumor of the human brain. It is characterized by invasive growth and strong resistance to treatment, and the median survival time of patients is 15 months. The invasive growth of this tumor type is associated with tumor cells with an aggressive phenotype, while its treatment resistance is att...

Objective: Sodium fluorescein (FL) is widely used as a fluorescent tracer for brain tumor resection. However, FL-guided resection of spinal gliomas has been reported only occasionally. To evaluate the safety, characteristics, and usefulness of FL-guided surgery in the resection of spinal glioma. Methods: Between January 2015 and December 2018, 220...

Glioblastoma (GB) is one of the most aggressive human brain tumors. The prognosis is unfavorable, its treatment is relatively ineffective, and the median survival is about 15 months. Medication development with new chemical compounds is one of the ways to solve the problem of current treatment inefficiency. This study is focused on the group of che...

Rationale: Glioblastoma multiforme (GBM) is one of the most aggressive human brain tumors. The prognosis is unfavorable with a median survival of 15 months. GBM aggressive nature is associated with a special phenotype of cancer cells that develops because of the transforming growth factor β (TGF-β). The study was aimed at providing experimental jus...

Objective: Application of Siwei Xiaoliuyin in glioma mice. Explore the effect of Siwei Xiaoliuyin on angiogenesis of nude mice glioma and its mechanism. Methods: Establish human glioma cell line U87 tumor model. Mice were randomized to the saline group, the conventional dose of Siwei Xiaoliuyin, high dose group of Siwei Xiaoliuyin, TMZ group, combi...

Glioblastoma multiforme is the most aggressive type of primary brain tumor in humans. Its invasive growth is associated with cluster of differentiation (CD)133 cancer stem cells (CSCs) and CD133⁻ differentiated glioblastoma cells (DGCs) with aggressive phenotype, which are developed under the influence of transforming growth factor (TGF)-β. The pre...

Twist is a transcription factor involved in the process of epithelial to mesenchymal transition (EMT) of carcinoma cells, and the promotion of invasion of gliomas through the mesenchymal adjusting process. However, its clinical significance in human glioma has not yet to be understood. To delineate the clinical-pathological significance and prognos...

Objective: To provide evidence for the mechanism of Chinese medicine to treat glioma. We observe the effects of Si wei xiao xiu yin combined with chemotherapy on the growth of subcutaneous xenografts in nude mice and the expression of miRNA-21 and miRNA-221 in tumor tissues. Methods: The subcutaneous transplantation model of nude mice was establish...

Gliomas are the most common malignant primary brain tumor, and their prognosis is extremely poor. Radiotherapy is an important treatment for glioma patients, but the changes caused by radiotherapy have brought difficulties in clinical image evaluation because differentiating glioma recurrence from post-radiotherapy changes including pseudo-progress...

Objective: To explore the strategy of surgical treatment of low-grade brain tumors associated with epilepsy. Methods: Clinical data of 158 patients with low-grade brain tumors were collected from January 2011 to December 2017 in Guangdong Sanjiu brain hospital. All patients received Preoperative evaluation. Lesion site: 18 cases were located in mul...

Glioblastoma Multiforme (GBM) is one the most common intracranial tumors discovered by Burns (1800) and Abernethy (1804) based on gross morphology of the autopsied material and referred to as “medullary sarcoma” and later “fungus medullare” (Abernethy, 1804; Burns, 1800). Virchow in 1863 was the first German pathologist using histomorphological tec...

Glioblastoma is one of the most aggressive human brain tumors. Even following all the modern protocols of complex treatment, the median patient survival typically does not exceed 15 months. This review analyzes the main reasons for glioblastoma resistance to therapy, as well as attempts at categorizing the main approaches to increasing chemotherapy...

Rationale: Glioblastoma multiforme (GBM) is the most aggressive primary glial brain tumor. The prognosis for GBM patients is not favorable, with the median survival time being 15 months. Its treatment resistance is associated with GBM cell population having cancer stem cells (CSCs). Wnt/β-catenin signaling pathway is a strategically important molec...

dl-3-n-butylphthalide (dl-NBP) is a powerful antioxidant compound with profound neuroprotective effects in stroke and brain injury. However, its role in Parkinson's disease (PD) is not well known. Traumatic brain injury (TBI) is one of the key factors in precipitating PD like symptoms in civilians and particularly in military personnel. Thus, it wo...

Mild traumatic brain injury (mTBI) is one of the leading predisposing factors in the development of Parkinson's disease (PD). Mild or moderate TBI induces rapid production of tau protein and alpha synuclein (ASNC) in the cerebrospinal fluid (CSF) and in several brain areas. Enhanced tau-phosphorylation and ASNC alters the molecular machinery of the...

Blast brain injury (bBI) is a combination of several forces of pressure, rotation, penetration of sharp objects and chemical exposure causing laceration, perforation and tissue losses in the brain. The bBI is quite prevalent in military personnel during combat operations. However, no suitable therapeutic strategies are available so far to minimize...

Introduction: In 2014 and 2015 Professor of neurology Andrey Bryukhovetskiy published a novel theory of the information-commutation organization of the human brain in Russia, China and the USA. The theory posits the hypothesis that the higher nervous activity (cognitive, intellectual, mnestic) of the humans and their mind are material and have micr...

Spinal cord evoked potentials (SCEP) are good indicators of spinal cord function in health and disease. Disturbances in SCEP amplitudes and latencies during spinal cord monitoring predict spinal cord pathology following trauma. Treatment with neuroprotective agents preserves SCEP and reduces cord pathology after injury. The possibility that cerebro...

Sleep deprivation (SD) is common in military personnel engaged in combat operations leading to brain dysfunction. Military personnel during acute or chronic SD often prone to traumatic brain injury (TBI) indicating the possibility of further exacerbating brain pathology. Several lines of evidence suggest that in both TBI and SD alpha-melanocyte-sti...

Glioma is the most common primary malignant brain tumor in adults and the patients have poor prognosis despite treatment with surgery, radiotherapy and chemotherapy. The anti-epileptic drug, valproic acid (VPA) as a HDAC inhibitors is often used in glioma patients even if the patients don't have brain tumors associated epilepsy (BAE). Some previous...

Traumatic brain injury (TBI) causes physical injury to the cell membranes of neurons, glial and axons causing the release of several neurochemicals including glutamate and cytokines altering cell-signaling pathways. Upregulation of mitogen associated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) occurs that is largely respon...

Rationale. Spasticity is one of the main complications after the spinal cord injury (SCI). Most commonly, severe cases of spasticity are treated surgically with intrathecal baclofen therapy (ITB). Spinal cord stimulation for chronic pains (SCS) serves as an alternative for ITB. Both methods have their benefits and limitations. This study is aimed a...

Introduction. Amyotrophic lateral sclerosis (ALS) is also known as motor neuron disease (MND) or Lou Gehrig's disease. It is a fatal neurodegenerative disease the cause of which is not clear. The effective therapy is absent. ALS is diagnosed through clinical examination and neurophysiologic tests. Clinically, the symptoms manifest when about 80% of...

Functional restoration after spinal cord injury (SCI) is one of the most challenging tasks in neurological clinical practice. With a view to exploring effective neurorestorative methods in the acute, subacute, and chronic phases of SCI, "Clinical Therapeutic Guidelines of Neurorestoration for Spinal Cord Injury (China Version 2016)" was first propo...

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Alzheimer's disease (AD) is estimated to be afflicting over 55 millions of individual worldwide in 2018–19 for which no suitable clinical therapeutic measures have been developed so far. Thus, there is an urgent need to explore novel therapeutic strategies using nanodelivery of drugs and agents either alone or in combination for superior neuroprote...

Concussive head injury (CHI) is quite prevalent in military personnel leading to lifetime disability in more than 85% of cases. Other reasons of CHI include motor vehicle accident, fall or blunt trauma under various conditions. In United States of America (USA) alone more than 150 k cases of head injury are added every year for which no suitable th...

Sleep deprivation (SD) is very common in military personnel resulting in mental anomalies and interfering with decision-making capabilities. Moreover during combat operation, these sleep-deprived soldiers often receive blunt head trauma casing concussive head injury (CHI). Recent observations clearly suggest that SD alone induces brain pathology an...

Parkinson's disease (PD) is affecting > 10 million people worldwide for which no suitable cure has been developed so far. Roughly, about two people per thousand populations are affected with PD like symptoms especially over the age of 50. About 1% of the populations above 60 years suffer from PD-like disease. The prevalence of the disease is increa...

Spinal cord injury (SCI) is a devastating disease inflicting lifetime disability to the victims. Military personnel are quite often victims of SCI for which no suitable therapeutic strategies have been developed so far. The main reason for SCI induced disability is loss of neural connections below and above the lesion site causing motor paralysis a...

Several lines of evidences show that anesthetics influence neurotoxicity and neuroprotection. The possibility that different anesthetic agents potentially influence the pathophysiological and functional outcome following neurotrauma was examined in a rat model of concussive head injury (CHI). The CHI was produced by an impact of 0.224N on the right...

Morphine withdrawal response is associated with brain edema formation, blood-brain barrier (BBB) disruption, activation of glial cells and heat shock protein (HSP 72kDa) responses in the CNS. Thus, exploration of suitable therapeutic measures is the need of the hour to induce neuroprotection in morphine withdrawal cases. There are reports that 5-HT...

Bradykinin is a mediator of vasogenic brain edema formation. Recent reports suggest that bradykinin interacts with nitric oxide synthase (NOS) system in the central nervous system (CNS). However, role of bradykinin in spinal cord injury (SCI) induced alterations in the blood-spinal cord barrier (BSCB), spinal cord blood flow (SCBF), edema formation...

Methamphetamine (METH) is a potent CNS stimulant that is widely used as a recreational drug. Due to its ability to increase bodily heat production and diminish heat loss due to peripheral vasoconstriction, METH is able to increase brain and body temperature. The hyperthermic effects of METH are potentiated when the drug is used under conditions of...

There is a growing trend of hypertension among military and civilian populations due to lifetime stressful situations. If hypertension is uncontrolled it leads to development of diabetes and serious neurological complications. Most of the World populations live in temperate zone across the World. Thus, a possibility exists that these hypertensive a...

5-Hydroxytryptophan (5-HTP), a precursor of serotonin, is therapeutically used for several psychiatric disorders such as anxiety and depression in the clinic. However, severe side effects, including abnormal mental functions, behavioral disturbances and intolerance are associated with this treatment. 5-HTP-induced elevation of plasma and brain sero...

Clinical neurorestorative therapies recently made great progress for patients with spinal cord injury (SCI). This paper systemically reviews historical perspectives, recent advancements and achievements in SCI through key neurorestorative strategies. In this study, a search was performed in the PubMed, Scopus, and Scholar Google search engines usin...