Abstract：
:After spinal cord injury (SCI), the majority of individuals develop spasticity, a debilitating condition involving involuntary movements, co-contraction of antagonistic muscles, and hyperreflexia. By acting on GABAergic and Ca2+-dependent signaling, current anti-spastic medications lead to serious side effects, including a drastic decrease in motoneuronal excitability which impairs motor function and rehabilitation efforts. Exercise, in contrast, decreases spastic symptoms without decreasing motoneuron excitability. These functional improvements coincide with an increase in expression of the chloride co-transporter KCC2 in lumbar motoneurons. Thus, we hypothesized that spastic symptoms can be alleviated directly through restoration of chloride homeostasis and endogenous inhibition by increasing KCC2 activity. Here, we used the recently developed KCC2 enhancer, CLP257, to evaluate the effects of acutely increasing KCC2 extrusion capability on spastic symptoms after chronic SCI. Sprague Dawley rats received a spinal cord transection at T12 and were either bike-trained or remained sedentary for 5 weeks. Increasing KCC2 activity in the lumbar enlargement improved the rate-dependent depression of the H-reflex and reduced both phasic and tonic EMG responses to muscle stretch in sedentary animals after chronic SCI. Furthermore, the improvements due to this pharmacological treatment mirror those of exercise. Together, our results suggest that pharmacologically increasing KCC2 activity is a promising approach to decrease spastic symptoms in individuals with SCI. By acting to directly restore endogenous inhibition, this strategy has potential to avoid severe side effects and improve the quality of life of affected individuals.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Bilchak JN,Yeakle K,Caron G,Malloy D,Côté MPdoi
10.1016/j.expneurol.2021.113605subject
Has Abstractpub_date
2021-01-13 00:00:00pages
113605eissn
0014-4886issn
1090-2430pii
S0014-4886(21)00010-8journal_volume
338pub_type
杂志文章abstract：:Traumatic brain injury (TBI) causes persistent neurologic deficits. Current therapies, predominantly focused upon cortical and hippocampal cellular survival, have limited benefit on cognitive outcomes. Striatal damage is associated with deficits in executive function, learning, and memory. Dopamine and cAMP regulated ...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2011.02.013
更新日期：2011-06-01 00:00:00
abstract：:Animal models treated with agricultural chemicals, such as rotenone, reproduce several degenerative features of human central nervous system (CNS) diseases. Glutamate is the most abundant excitatory amino acid transmitter in the mammalian central nervous system and its transmission is implicated in a variety of brain ...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2007.09.023
更新日期：2008-01-01 00:00:00
abstract：:The gastrointestinal tract of vertebrates is a heterogeneous organ system innervated to varying degrees by a local enteric neural network as well as extrinsic parasympathetic and sympathetic neural circuits located along the brainstem and spinal axis. This diverse organ system serves to regulate the secretory and prop...
journal_title：Experimental neurology
pub_type： 杂志文章,评审
doi：10.1016/j.expneurol.2019.113009
更新日期：2019-10-01 00:00:00
abstract：:the antiexcitotoxic efficacy of melatonin, a putative endogenous hydroxyl radical scavenger, was studied in primary cultures of rat cerebellar granule neurons. Excitotoxicity was induced in 7- to 9-day-old cultures by an exposure to glutamate (15 min in the absence of magnesium) or to glutamate receptor agonists, kain...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(95)90005-5
更新日期：1995-01-01 00:00:00
abstract：:Dopaminergic (DAergic) hypofunction in the medial prefrontal cortex (mPFC) has been implicated in the negative and cognitive symptoms of schizophrenia and is regulated by serotonergic (5-HTergic) neurons in the dorsal raphe nucleus (DRN). The lateral habenula (LHb) is a key element in controlling DRN 5-HT neurons. We ...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2019.05.005
更新日期：2019-08-01 00:00:00
abstract：:Bilateral lesions of the ventromedial nucleus of the hypothalamus (VMN) significantly attentuated lordosis behavior in the female rat. The degree of this deficit was significantly correlated with the amount of damage to the VMN. There was no improvement in lordosis performance even after an extended recovery period. ...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(83)90035-3
更新日期：1983-03-01 00:00:00
abstract：:Neuronal apoptosis is a central pathological process in subarachnoid hemorrhage (SAH)-induced early brain injury. Previous studies indicated that ErbB4 (EGFR family member v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) is essential for normal development and maintenance of the nervous system. In this...
journal_title：Experimental neurology
pub_type： 杂志文章
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更新日期：2017-11-01 00:00:00
abstract：:Copyright ...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1998.6843
更新日期：1998-06-01 00:00:00
abstract：:The ST14A cell line was previously derived from embryonic day 14 rat striatal primordia by retroviral transduction of the temperature-sensitive SV40 large T antigen. We showed that cell division and expression of nestin persists at 33 degrees C, the permissive temperature, whereas cell division ceases, nestin expressi...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.2000.7551
更新日期：2001-02-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2020.113386
更新日期：2020-10-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2006.02.134
更新日期：2006-08-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2008.09.018
更新日期：2009-01-01 00:00:00
abstract：:We recently revealed a unique glycan on the Fc domain of IgG antibodies in ALS patients that mediates antibody-dependent cell cytotoxicity (ADCC). This glycan has a bi-antennary structure that lacks the core fucose and sialic acid residues but contains a bisecting GlcNAc (A2BG2). Little is known, however, about the in...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2015.02.023
更新日期：2015-05-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(86)90307-9
更新日期：1986-06-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2015.03.004
更新日期：2015-05-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.2002.7926
更新日期：2002-07-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.2000.7362
更新日期：2000-05-01 00:00:00
abstract：:A graded contusion spinal cord injury (SCI) was created in the adult rat spinal cord using the Infinite Horizons (IH) impactor to study the correlation between injury severity and anatomical, behavioral, and electrophysiological outcomes. Adult Fisher rats were equally divided into five groups and received contusion i...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2004.08.026
更新日期：2005-02-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1995.1097
更新日期：1995-12-01 00:00:00
abstract：:Paired corticospinal-motoneuronal stimulation (PCMS) elicits spinal synaptic plasticity in humans with chronic incomplete cervical spinal cord injury (SCI). Here, we examined whether PCMS-induced plasticity could be potentiated by acute intermittent hypoxia (AIH), a treatment also known to induce spinal synaptic plast...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2020.113483
更新日期：2021-01-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章,评审
doi：10.1016/j.expneurol.2009.11.019
更新日期：2010-09-01 00:00:00
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journal_title：Experimental neurology
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1996.0115
更新日期：1996-07-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(83)90005-5
更新日期：1983-04-01 00:00:00
abstract：:An increasing body of research suggests that a number of immune mechanisms play a role in degenerative pathways in Parkinson's disease (PD). In the current work we investigated a posited humoral immune response in this disorder. Sera from PD patients exhibited a significantly enhanced absorbance response on a novel EL...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2009.03.002
更新日期：2009-06-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2006.08.003
更新日期：2007-01-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2005.01.014
更新日期：2005-06-01 00:00:00
abstract：:Frontotemporal dementia (FTD) is the second most common cause of presenile dementia. Here we have investigated the frequency of the epsilon4 allele of the Apolipoprotein (APOE) gene in FTD and in other non-Alzheimer forms of dementia related to FTD such as Motor Neurone disease dementia, semantic dementia, progressive...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.2000.7387
更新日期：2000-06-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(87)90314-1
更新日期：1987-03-01 00:00:00
abstract：:Muscular dystrophies (MDs) consist of a genetically heterogeneous group of disorders, recessive or dominant, characterized by progressive skeletal muscle weakening. To date, no effective treatment is available. Experimental strategies pursuing muscle regeneration through the transplantation of stem cell preparations h...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2009.08.002
更新日期：2009-11-01 00:00:00
