Abstract:
:Traumatic axonal injury (TAI) evolves within minutes to hours following traumatic brain injury (TBI). Previous studies have identified axolemmal disruption and impaired axonal transport (AxT) as key mechanisms in the evolution of TAI. While initially hypothesized that axolemmal disruption culminates in impaired AxT, previous studies employed single-label methodologies that did not allow for a full determination of the spatial-temporal relationships of these two events. To explore directly the relationship between impaired AxT and altered axolemmal permeability, the current investigation employed 40, 10, and 3 kDa fluorescently conjugated dextrans as markers of axolemmal integrity, with antibodies targeting the anterogradely transported amyloid precursor protein (APP) utilized as a marker of impaired AxT. Rats underwent impact acceleration TBI and were intrathecally administered 40 kDa, 40 + 10 kDa or 40 + 3 kDa fluorescently tagged dextrans, with brains subsequently prepared for APP immunofluorescence. Brainstem corticospinal tracts (CSpT), medial lemnisci (ML), and medial longitudinal fasciculi were examined for evidence of TAI. APP and all dextrans consistently localized to distinct classes of TAI. Dextrans were noted as early as 5 min following injury within axonal segments demonstrating an irregular/tortuous appearance, and were seen within thin and elongate/vacuolated axons by 30 min-6 h following injury. APP, first noted within swollen axons at 30 min following injury, was found within progressively swollen axons that showed no dextran colocalization within 3 h of injury. However, by 6 h, dextrans colocalized in disconnected axonal bulbs. At this time-point, dextrans also persisted within single-labeled, highly vacuolated/thin, and elongate axons. These studies confirm that axolemmal disruption and impaired AxT occur as distinct non-related events early in the pathogenesis of TAI. Further, these studies provide evidence that the process of impaired axonal transport and subsequent axonal disconnection leads to delayed axolemmal instability, rather than proceeding as a consequence of initial axolemmal failure. This finding underscores the need of multiple approaches to fully assess the axonal response to TBI.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Stone JR,Okonkwo DO,Dialo AO,Rubin DG,Mutlu LK,Povlishock JT,Helm GAdoi
10.1016/j.expneurol.2004.05.022keywords:
subject
Has Abstractpub_date
2004-11-01 00:00:00pages
59-69issue
1eissn
0014-4886issn
1090-2430pii
S0014488604002080journal_volume
190pub_type
杂志文章abstract::Convection-enhanced delivery has recently entered the clinic and represents a promising new therapeutic option in the field of neurodegenerative diseases and treatment of brain tumors. Understanding of the principles governing delivery and flow of macromolecules within the CNS is still poorly understood and requires m...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2005.07.009
更新日期:2005-11-01 00:00:00
abstract::Children who are born preterm are at risk for encephalopathy of prematurity, a leading cause of cerebral palsy, cognitive delay and behavioral disorders. Current interventions are limited and none have been shown to reverse cognitive and behavioral impairments, a primary determinant of poor quality of life for these c...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2017.12.010
更新日期:2018-04-01 00:00:00
abstract::The age-dependent effects of sympathetic superior cervical ganglionectomy on smooth muscle alpha-adrenoceptor contractile responses were investigated in Müller's muscle in the superior eyelid of the Sprague-Dawley rat. Ganglionectomies in juvenile (32 days) and adult (70 days) rats produced sustained sympathetic dener...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(86)90031-2
更新日期:1986-01-01 00:00:00
abstract::At the age of 31 days, Long-Evans female rats received electrolytic lesions either of the medial fimbria (N = 24), of the dorsal subcallosal fornix (N = 24), or of both structures (N = 24). Ten rats were used as sham-operated controls. Ten days later, half the rats of each lesion group received intrahippocampal grafts...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(87)90114-2
更新日期:1987-09-01 00:00:00
abstract::Massive increases in extracellular dopamine have been reported in the ischemic rodent striatum, implicating this neurotransmitter in toxic events. We have examined whether dopamine receptor antagonists are protective against hypoxic insult, using brain slices containing the rostral striatum obtained from adult male C5...
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
abstract::We conducted a quantitative study of the trochlear motoneurons and the myotube clusters in the corresponding superior oblique muscle of the Japanese quail, before, during, and after the period of normally occurring motoneuron degeneration. A ratio of approximately 1:1 between myotube clusters and neurons was observed ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(85)90063-9
更新日期:1985-10-01 00:00:00
abstract::Olfactory ensheathing cells (OEC) constitute a specialized population of glia that accompany primary olfactory axons and have been reported to facilitate axonal regeneration after spinal cord injury in vivo. In the present report we describe OEC neurotrophic factor expression and neurotrophic properties of OECs in vit...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/s0014-4886(02)00058-4
更新日期:2003-04-01 00:00:00
abstract::Peripheral nerves have the unique capability to regenerate after injury. Insights into regeneration of peripheral nerves after injury may have implications for neurodegenerative diseases of the nervous system. In this study, we analyzed the expression and function of desmoplakin in peripheral nerve regeneration. Desmo...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2014.12.005
更新日期:2015-02-01 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::C2 spinal cord hemisection results in synaptic and astroglial changes in the phrenic nucleus which have been associated with the recovery of the ipsilateral hemidiaphragm during expression of the crossed phrenic phenomenon. As part of our ongoing analysis of the neurotransmitters involved, the present study investigat...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1999.7238
更新日期:1999-12-01 00:00:00
abstract::A prospective, multicenter, randomized trial did not demonstrate improved outcomes in severe traumatic brain injured patients treated with mild hypothermia [Clifton, G.L., Miller, E.R., Choi, S.C., Levin, H.S., McCauley, S., Smith, K.R., Jr., Muizelaar, J.P., Wagner, F.C., Jr., Marion, D.W., Luerssen, T.G., Chesnut, R...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2008.09.024
更新日期:2009-01-01 00:00:00
abstract::Overt behavioral symptoms of Parkinson's disease (PD) do not occur until over 80% of the striatal dopamine content has been lost. Diagnosis of the disorder relies on identifying clinical symptoms including akinesia, resting tremor, and rigidity. In retrospect, behavioral deficits are observed several years prior to di...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2002.8021
更新日期:2002-11-01 00:00:00
abstract::Demyelinating diseases comprise a spectrum of immunopathologic syndromes in which myelin, the fatty covering of nerve cell fibers in the brain and spinal cord, is destroyed. In this study, we have shown for the first time that ocular infection of BALB/c mice with a recombinant herpes simplex virus type 1 (HSV-1) expre...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2004.12.004
更新日期:2005-05-01 00:00:00
abstract::Unit activity related to a go/no-go visual discrimination task was studied in four rhesus monkeys. We recorded 272 task-related cells from frontal cortex in a region extending from the midprincipal sulcus to the central sulcus, and medially to the cingulate sulcus. Units located in anterior regions (dorsolateral prefr...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(87)90213-5
更新日期:1987-06-01 00:00:00
abstract::A host protein encoded by the gene specifying the scrapie amyloid precursor affects pathogenesis of the transmissible spongiform encephalopathies: Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker's syndrome (GSS), and kuru in man, and scrapie in animals. We found a mutation in this gene of two patients ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(89)90095-2
更新日期:1989-11-01 00:00:00
abstract::We evaluated the effects of allogeneic bone marrow stromal cell treatment of stroke on functional outcome, glial-axonal architecture, and immune reaction. Female Wistar rats were subjected to 2 h of middle cerebral artery occlusion. Rats were injected intravenously with PBS, male allogeneic ACI--or syngeneic Wistar--b...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2005.11.029
更新日期:2006-04-01 00:00:00
abstract::The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which produces Parkinsonism, is mediated by its metabolite 1-methyl-4-phenylpyridinium ion (MPP+). When injected into the striatum MPP+ is accumulated by dopaminergic nerve terminals and is then retrogradely transported to the substantia nigra compacta...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6416
更新日期:1997-03-01 00:00:00
abstract::Vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) in dorsal root ganglia (DRGs) are known to be upregulated and to contribute to the mechanisms of neuropathic pain following peripheral nerve injury. Moreover, transcription factor c-Jun regulates the expressions of both VIP and NPY in cultured DRG neurons. T...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2006.09.020
更新日期:2007-03-01 00:00:00
abstract::Human immunodeficiency virus (HIV) patients treated with nucleoside reverse transcriptase inhibitors (NRTIs), have been known to develop neuropathic pain. While there has been a major shift away from some neurotoxic NRTIs in current antiretroviral therapy, a large number of HIV patients alive today have previously rec...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2016.04.012
更新日期:2016-07-01 00:00:00
abstract::The sciatic nerve of the rat is a commonly used model for studies on nerve injury, regeneration, and recovery of function. To interpret the changes that occur in a neuron population subsequent to peripheral nerve injury, and to compare different repair procedures, it is essential to have a complete and accurate unders...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(86)90161-5
更新日期:1986-07-01 00:00:00
abstract::Ibuprofen is commonly used as an anti-inflammatory analgesic drug, although it is not amongst the first-line treatments for neuropathic pain. Its main effects are mediated by non-specific inhibition of COX enzymes, but it also exerts some COX-independent effects, such as the inhibition of RhoA signaling and the modula...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2013.11.008
更新日期:2014-02-01 00:00:00
abstract::Quisqualate (Quis) and other excitotoxins such as ibotenate and N-methyl aspartate, have been used to destroy neurons in the area of the nucleus basalis magnocellularis (NBM) in order to study the relationship between loss of cholinergic neurons in the basal forebrain and various behavioral deficits, including learnin...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1994.1046
更新日期:1994-03-01 00:00:00
abstract::Multiple system atrophy (MSA) is a rare neurodegenerative disease of undetermined cause manifesting with progressive autonomic failure (AF), cerebellar ataxia and parkinsonism due to neuronal loss in multiple brain areas associated with (oligodendro)glial cytoplasmic alpha-synuclein (alpha SYN) inclusions (GCIs). Usin...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2010.05.008
更新日期:2010-08-01 00:00:00
abstract::The basis for neuronal dysfunction following inflammatory demyelination of the central nervous system (CNS) remains poorly understood. We characterized the network response to white matter injury in the anterior visual pathway using an experimental model of optic neuritis (ON), as ON is often an early manifestation of...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2017.05.004
更新日期:2017-09-01 00:00:00
abstract::Astrocytes react to CNS injury by building a dense wall of filamentous processes around the lesion. Stromal cells quickly take up residence in the lesion core and synthesize connective tissue elements that contribute to fibrosis. Oligodendrocyte precursor cells proliferate within the lesion and entrap dystrophic axon ...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1016/j.expneurol.2013.12.024
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:Cognitive impairment in humans with Alzheimer's disease (AD) and in animal models of Aβ-pathology can be ameliorated by treatments with the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ) agonists, such as rosiglitazone (RSG). Previously, we demonstrated that in the Tg2576 animal mo...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2017.05.005
更新日期:2017-09-01 00:00:00
abstract::Parkinson's disease (PD) is an aging-associated neurodegenerative disorder with progressive pathology involving the loss of midbrain dopaminergic neurons. Neurotrophic factors are promising for PD gene therapy; they are integrally involved in the development of the nigrostriatal system. Cerebral dopamine neurotrophic ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2013.06.002
更新日期:2013-10-01 00:00:00
abstract::It has been suggested that the increased transient expression of immediate-early gene transcription factors seen in nerve cells following an afterdischarge may initiate longer lasting or permanent changes in gene expression which underly the development of kindling. Since the development of kindling is sensitive to ph...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1994.1137
更新日期:1994-08-01 00:00:00
abstract::Although brain pathways activated by sepsis may respond acutely to endotoxin administration, the long-term central response to sepsis is not known. We prepared male rats for hormonal sampling at the circadian nadir (AM) and peak (PM) after cecal ligation and puncture (CLP) or sham surgery. Diurnal variation of cortico...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2007.03.015
更新日期:2007-06-01 00:00:00
abstract::Our primary aim was to determine if there exists a preferential involvement of the fast-twitch or slow-twitch skeletal muscle fibers in the dy2J/dy2J strain of murine dystrophy. The changes in the contractile properties of the slow-twitch soleus (SOL) and the fast-twitch extensor digitorum longus (EDL) muscles of norm...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(83)90297-2
更新日期:1983-05-01 00:00:00