The Experts below are selected from a list of 870 Experts worldwide ranked by ideXlab platform

Hari Shanker Sharma - One of the best experts on this subject based on the ideXlab platform.

  • anesthetics influence concussive head injury induced blood brain barrier breakdown brain edema formation cerebral blood flow serotonin levels brain pathology and functional outcome
    International Review of Neurobiology, 2019
    Co-Authors: Hari Shanker Sharma, Dafin F Muresanu, Ala Nozari, Rudy J Castellani, Lars Wiklund, Aruna Sharma
    Abstract:

    Abstract 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 0.224 N on the right parietal bone by dropping a weight of 114.6 g from a 20 cm height under different anesthetic agents, e.g., inhaled ether anesthesia or intraperitoneally administered ketamine, pentobarbital, Equithesin or urethane anesthesia. Five hour CHI resulted in profound volume swelling and brain edema formation in both hemispheres showing disruption of the blood-brain barrier (BBB) to Evans blue and radioiodine. A marked decrease in the cortical CBF and a profound increase in plasma or brain serotonin levels were seen at this time. Neuronal damages were present in several parts of the brain. These pathological changes were most marked in CHI under ether anesthesia followed by ketamine (35 mg/kg, i.p.), pentobarbital (50 mg/kg, i.p.), Equithesin (3 mL/kg, i.p.) and urethane (1 g/kg, i.p.). The functional outcome on Rota Rod performances or grid walking tests was also most adversely affected after CHI under ether anesthesia followed by pentobarbital, Equithesin and ketamine. Interestingly, the plasma and brain serotonin levels strongly correlated with the development of brain edema in head injured animals in relation to different anesthetic agents used. These observations suggest that anesthetic agents are detrimental to functional and pathological outcomes in CHI probably through influencing the circulating plasma and brain serotonin levels, not reported earlier. Whether anesthetics could also affect the efficacy of different neuroprotective agents in CNS injuries is a new subject that is currently being examined in our laboratory.

  • neuroprotective effects of a potent bradykinin b2 receptor antagonist hoe 140 on microvascular permeability blood flow disturbances edema formation cell injury and nitric oxide synthase upregulation following trauma to the spinal cord
    International Review of Neurobiology, 2019
    Co-Authors: Hari Shanker Sharma, Dafin F Muresanu, Rudy J Castellani, Lianyuan Feng, Aruna Sharma
    Abstract:

    Abstract 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 and cell changes are still not well known. Our previous reports showed that SCI induces marked upregulation of neuronal NOS (nNOS) in the cord associated with BSCB disruption, edema formation and cell injury. Thus, a possibility exists that bradykinin participates in SCI induced nNOS upregulation and cord pathology. To explore this idea a potent bradykinin B2 receptor antagonist HOE-140 was used in our rat model of SCI and cord pathology. SCI was inflicted in Equithesin anesthetized rats by making a longitudinal incision (2 mm deep and 5 mm long) into the right dorsal horn of the T10-11 segment. The animals were allowed to survive 5 h after injury. A focal SCI significantly disrupted BSCB to Evans blue and [131] I-sodium in the traumatized and adjacent segments. Interestingly, far remote spinal cord segments C4 and T5 segments also affected within 5 h. These spinal cord segments also exhibited pronounced reductions in the SCBF (mean—30%), increased edematous swelling and profound neuronal damages. Upregulation of nNOS expression is seen in both the dorsal and ventral horns of the spinal cord exhibiting cord pathology. At the ultrastructural level, exudation of lanthanum is seen within the endothelial cell cytoplasm and occasionally in the basal lamina. Pretreatment with low doses of HOE-140 (0. 1 mg to 1 mg/kg, i.v.) 30 min prior to SCI significantly enhanced the SCBF and reduced the BSCB disruption, edema formation, nNOS upregulation and cell injury. However, HOE-140 in doses ranging from 2 mg to 5 mg/kg, i.v. did not induce significant neuroprotection. These observations are the first to suggest that bradykinin B2 receptors play an important role in BSCB permeability, SCBF, edema formation, nNOS upregulation and cell injury following acute SCI, not reported earlier.

  • cerebrolysin reduces blood cerebrospinal fluid barrier permeability change brain pathology and functional deficits following traumatic brain injury in the rat
    Annals of the New York Academy of Sciences, 2010
    Co-Authors: Hari Shanker Sharma, Sibilla Zimmermannmeinzingen, Conrad E Johanson
    Abstract:

    Traumatic brain injuries (TBIs) induce profound breakdown of the blood-brain and blood-cerebrospinal fluid barriers (BCSFB), brain pathology/edema, and sensory-motor disturbances. Because neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and glial cell-derived neurotrophic factor (GDNF), are neuroprotective in models of brain and spinal cord injuries, we hypothesized that a combination of neurotrophic factors would enhance neuroprotective efficacy. In the present investigation, we examined the effects of Cerebrolysin, a mixture of different neurotrophic factors (Ebewe Neuro Pharma, Austria) on the brain pathology and functional outcome in a rat model of TBI. TBI was produced under Equithesin (3 mL/kg, i.p.) anesthesia by making a longitudinal incision into the right parietal cerebral cortex. Untreated injured rats developed profound disruption of the blood-brain barrier (BBB) to proteins, edema/cell injury, and marked sensory-motor dysfunctions on rota-rod and grid-walking tests at 5 h TBI. Intracerebroventricular administration of Cerebrolysin (10 or 30 μL) either 5 min or 1 h after TBI significantly reduced leakage of Evans blue and radioiodine tracers across the BBB and BCSFB, and attenuated brain edema formation/neuronal damage in the cortex as well as underlying subcortical regions. Cerebrolysin-treated animals also had improved sensory-motor functions. However, administration of Cerebrolysin 2 h after TBI did not affect these parameters significantly. These observations in TBI demonstrate that early intervention with Cerebrolysin reduces BBB and BCSFB permeability changes, attenuates brain pathology and brain edema, and mitigates functional deficits. Taken together, our observations suggest that Cerebrolysin has potential therapeutic value in TBI.

Aruna Sharma - One of the best experts on this subject based on the ideXlab platform.

  • anesthetics influence concussive head injury induced blood brain barrier breakdown brain edema formation cerebral blood flow serotonin levels brain pathology and functional outcome
    International Review of Neurobiology, 2019
    Co-Authors: Hari Shanker Sharma, Dafin F Muresanu, Ala Nozari, Rudy J Castellani, Lars Wiklund, Aruna Sharma
    Abstract:

    Abstract 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 0.224 N on the right parietal bone by dropping a weight of 114.6 g from a 20 cm height under different anesthetic agents, e.g., inhaled ether anesthesia or intraperitoneally administered ketamine, pentobarbital, Equithesin or urethane anesthesia. Five hour CHI resulted in profound volume swelling and brain edema formation in both hemispheres showing disruption of the blood-brain barrier (BBB) to Evans blue and radioiodine. A marked decrease in the cortical CBF and a profound increase in plasma or brain serotonin levels were seen at this time. Neuronal damages were present in several parts of the brain. These pathological changes were most marked in CHI under ether anesthesia followed by ketamine (35 mg/kg, i.p.), pentobarbital (50 mg/kg, i.p.), Equithesin (3 mL/kg, i.p.) and urethane (1 g/kg, i.p.). The functional outcome on Rota Rod performances or grid walking tests was also most adversely affected after CHI under ether anesthesia followed by pentobarbital, Equithesin and ketamine. Interestingly, the plasma and brain serotonin levels strongly correlated with the development of brain edema in head injured animals in relation to different anesthetic agents used. These observations suggest that anesthetic agents are detrimental to functional and pathological outcomes in CHI probably through influencing the circulating plasma and brain serotonin levels, not reported earlier. Whether anesthetics could also affect the efficacy of different neuroprotective agents in CNS injuries is a new subject that is currently being examined in our laboratory.

  • neuroprotective effects of a potent bradykinin b2 receptor antagonist hoe 140 on microvascular permeability blood flow disturbances edema formation cell injury and nitric oxide synthase upregulation following trauma to the spinal cord
    International Review of Neurobiology, 2019
    Co-Authors: Hari Shanker Sharma, Dafin F Muresanu, Rudy J Castellani, Lianyuan Feng, Aruna Sharma
    Abstract:

    Abstract 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 and cell changes are still not well known. Our previous reports showed that SCI induces marked upregulation of neuronal NOS (nNOS) in the cord associated with BSCB disruption, edema formation and cell injury. Thus, a possibility exists that bradykinin participates in SCI induced nNOS upregulation and cord pathology. To explore this idea a potent bradykinin B2 receptor antagonist HOE-140 was used in our rat model of SCI and cord pathology. SCI was inflicted in Equithesin anesthetized rats by making a longitudinal incision (2 mm deep and 5 mm long) into the right dorsal horn of the T10-11 segment. The animals were allowed to survive 5 h after injury. A focal SCI significantly disrupted BSCB to Evans blue and [131] I-sodium in the traumatized and adjacent segments. Interestingly, far remote spinal cord segments C4 and T5 segments also affected within 5 h. These spinal cord segments also exhibited pronounced reductions in the SCBF (mean—30%), increased edematous swelling and profound neuronal damages. Upregulation of nNOS expression is seen in both the dorsal and ventral horns of the spinal cord exhibiting cord pathology. At the ultrastructural level, exudation of lanthanum is seen within the endothelial cell cytoplasm and occasionally in the basal lamina. Pretreatment with low doses of HOE-140 (0. 1 mg to 1 mg/kg, i.v.) 30 min prior to SCI significantly enhanced the SCBF and reduced the BSCB disruption, edema formation, nNOS upregulation and cell injury. However, HOE-140 in doses ranging from 2 mg to 5 mg/kg, i.v. did not induce significant neuroprotection. These observations are the first to suggest that bradykinin B2 receptors play an important role in BSCB permeability, SCBF, edema formation, nNOS upregulation and cell injury following acute SCI, not reported earlier.

P. O. Sjöquist - One of the best experts on this subject based on the ideXlab platform.

  • Spinal cord injury induced heat shock protein expression is reduced by an antioxidant compound H-290/51. An experimental study using light and electron microscopy in the rat
    Journal of Neural Transmission, 2006
    Co-Authors: H. S. Sharma, T. Gordh, L. Wiklund, S. Mohanty, P. O. Sjöquist
    Abstract:

    The possibility that oxidative stress participates in heat shock protein 72 kD (HSP 72) expression following a focal trauma to the spinal cord was examined using a potent antioxidant compound H-290/51 in a rat model. A focal spinal cord injury (SCI) inflicted by making a longitudinal incision on the right dorsal horn of the T10–T11 segment under Equithesin anaesthesia resulted in profound upregulation of HSP 72 expression in the adjacent spinal cord segments T9 and T12. This expression of HSP was most marked in the ipsilateral cord at 5 h after SCI. Pretreatment with H-290/51 (50 mg/kg, p.o.) 30 min before SCI markedly attenuated HSP expression in the spinal cord seen at 5 h. The motor functions of traumatized rats were also improved in the drug treated group. At this time, structural changes in the spinal cord and edema formation were considerable reduced compared to the untreated traumatized rats. Taken together, these observations suggest that (i) oxidative stress participates in HSP response following trauma, and (ii) the antioxidant compound H-290/51 attenuates cellularstress, improves motor functions and induces considerable neuroprotection in the early phase of SCI. Further studies using post-injury treatment with H-290/51 is needed to explore its therapeutic potentials in clinical settings.

Lindsey, Charles Julian - One of the best experts on this subject based on the ideXlab platform.

  • Estudo ultraestrutural de degeneração transneuronal dos elementos axonais do núcleo paratrigeminal de ratos com desnervação sino-aórtica
    'FapUNIFESP (SciELO)', 2012
    Co-Authors: Caous, Cristofer André, Smith, Ricardo Luiz, Freymüller-haapalainen Edna, Lindsey, Charles Julian
    Abstract:

    OBJECTIVE: Morphological study that searched to authenticate the presence of sinoaortic baroreceptor inputs within the dorsolateral medullary nucleus under electron microscopy analysis. METHODS: After a 5-day survival period, 9 baroreceptor-denervated rats deeply anaesthetized with Equithesin were transcardially perfused and their brains were histologically processed. RESULTS: The neuronal cytoarchitecture of the paratrigeminal nucleus comprehends afferent projections from other nuclei that have a distributive character regarding visceral and nociceptive functions in the cardiovascular reflex integration response. CONCLUSION: The medial portion of the nucleus receives afferent projections of the rostral ventrolateral medulla, as shown by retrograde neurotracing studies. The present results show that the medial extent of the paratrigeminal nucleus contains degenerated axoplasmic cellular components in sinoaortic deafferented rats. The number of degenerated axonal fibers was also larger in this area of the nucleus.OBJETIVO: Estudo morfológico que buscou verificar, por meio de microscopia eletrônica, a presença de aferências de receptores sino-aórticos em núcleo localizado na região dorso-lateral bulbar. MÉTODOS: Após 5 dias de sobrevida, 9 ratos com desnervação sino-aórtica anestesiados com equitesina foram submetidos à perfusão transcardíaca, e o encéfalo de cada um deles foi processado histologicamente. RESULTADOS: A citoarquitetura neuronal do núcleo paratrigeminal compreende projeções aferentes de outros núcleos que apresentam uma característica distributiva em relação às funções viscerais e nociceptivas na integração do reflexo cardiovascular. CONCLUSÃO: A porção medial do núcleo recebe projeções aferentes da região rostro-ventrolateral do troncoencefálico, confirmadas por meio de estudos com rastreadores neuronais. Os resultados indicam que a região medial do núcleo paratrigeminal contém o maior número de fibras axonais degeneradas.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Hospital Israelita Albert Einstein Instituto do CérebroUniversidade Federal de São Paulo (UNIFESP)Universidade Federal de São Paulo (UNIFESP) Centro de Microscopia EletrônicaUNIFESP, Centro de Microscopia EletrônicaSciEL

Lindsey, Charles Julian [unifesp] - One of the best experts on this subject based on the ideXlab platform.

  • Estudo ultraestrutural de degeneração transneuronal dos elementos axonais do núcleo paratrigeminal de ratos com desnervação sino-aórtica
    Instituto Israelita de Ensino e Pesquisa Albert Einstein, 2012
    Co-Authors: Caous, Cristofer André [unifesp], Smith, Ricardo Luiz [unifesp], Freymüller-haapalainen, Edna [unifesp], Lindsey, Charles Julian [unifesp]
    Abstract:

    OBJECTIVE: Morphological study that searched to authenticate the presence of sinoaortic baroreceptor inputs within the dorsolateral medullary nucleus under electron microscopy analysis. METHODS: After a 5-day survival period, 9 baroreceptor-denervated rats deeply anaesthetized with Equithesin were transcardially perfused and their brains were histologically processed. RESULTS: The neuronal cytoarchitecture of the paratrigeminal nucleus comprehends afferent projections from other nuclei that have a distributive character regarding visceral and nociceptive functions in the cardiovascular reflex integration response. CONCLUSION: The medial portion of the nucleus receives afferent projections of the rostral ventrolateral medulla, as shown by retrograde neurotracing studies. The present results show that the medial extent of the paratrigeminal nucleus contains degenerated axoplasmic cellular components in sinoaortic deafferented rats. The number of degenerated axonal fibers was also larger in this area of the nucleus.OBJETIVO: Estudo morfológico que buscou verificar, por meio de microscopia eletrônica, a presença de aferências de receptores sino-aórticos em núcleo localizado na região dorso-lateral bulbar. MÉTODOS: Após 5 dias de sobrevida, 9 ratos com desnervação sino-aórtica anestesiados com equitesina foram submetidos à perfusão transcardíaca, e o encéfalo de cada um deles foi processado histologicamente. RESULTADOS: A citoarquitetura neuronal do núcleo paratrigeminal compreende projeções aferentes de outros núcleos que apresentam uma característica distributiva em relação às funções viscerais e nociceptivas na integração do reflexo cardiovascular. CONCLUSÃO: A porção medial do núcleo recebe projeções aferentes da região rostro-ventrolateral do troncoencefálico, confirmadas por meio de estudos com rastreadores neuronais. Os resultados indicam que a região medial do núcleo paratrigeminal contém o maior número de fibras axonais degeneradas