Abstract:
:In the neocortex, the effectiveness of potential transplantation therapy for diseases involving neuronal loss may depend upon whether donor neurons can reestablish the precise long-distance projections that form the basis of sensory, motor, and cognitive function. During corticogenesis, the formation of these connections is affected by tropic factors, extracellular matrix, structural pathways, and developmental cell death. Previous studies demonstrated that embryonic neurons and multipotent neural precursors transplanted into neocortex or mice undergoing photolytically induced, synchronous, apoptotic neuronal degeneration selectively migrate into these regions, where they differentiate into pyramidal neurons and accept afferent synaptic input. The experiments presented here assess whether embryonic neurons transplanted into regions of somatosensory cortex undergoing targeted cell death differentiate further and develop long-distance axons and whether this outgrowth is target specific. Neocortical neurons from Gestational Day 17 mouse embryos were dissociated, prelabeled with fluorescent nanospheres and a lipophilic dye (DiI or PKH), and transplanted into adult mouse primary somatosensory cortex (S1) undergoing apoptotic degeneration of callosal projection neurons. Donor neurons selectively migrated into and differentiated within regions of targeted neuronal death in lamina II/III over a 2-week period, in agreement with our prior studies. To detect possible projections made by donor neurons 2, 4, 6, 8, or 10 weeks following transplantation, the retrogradely transported dye fluorogold (FG) was stereotaxically injected into contralateral S1, ipsilateral secondary somatosensory cortex (S2), or ipsilateral thalamus. Ten weeks following transplantation, 21 +/- 5% of the labeled donor neurons were labeled by FG injections into contralateral S1, demonstrating that donor neurons sent projections to the distant area, the original target of host neurons undergoing photolytically induced cell death. No donor neurons were labeled with FG injections into ipsilateral S2 or thalamus, nearby targets of other subpopulations of neurons in S1. These data indicate that in the adult neocortex: (1) transplanted immature neurons are capable of extending long-distance projections between hemispheres through the mature white matter of the corpus callosum and (2) these projections are formed with specificity to replace projections by neurons undergoing synchronous degeneration. These experiments provide an experimental system with which to test factors affecting such outgrowth and connectivity. Taken together, these results suggest that the reconstruction and repair of cortical circuitry responsible for sensory, motor, or cognitive function may be possible in the mature neocortex, if donor neurons or precursor cells are provided with the correct combination of local and distant signals within an appropriately permissive host environment.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Hernit-Grant CS,Macklis JDdoi
10.1006/exnr.1996.0088subject
Has Abstractpub_date
1996-05-01 00:00:00pages
131-42issue
1eissn
0014-4886issn
1090-2430pii
S0014-4886(96)90088-6journal_volume
139pub_type
杂志文章abstract::Rats were injected with progressively increasing doses of morphine or meperidine during a period of 3 to 40 days. From this colony of animals individual rats were used at 3- to 4-day intervals for electrophysiologic experiments to analyze the activity of nociceptive neurons in the somesthetic thalamus. After an i.p. i...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(84)90051-7
更新日期:1984-01-01 00:00:00
abstract::Golgi and computer morphometric analysis of neuronal dendrites was done on four cases, one each of Tay-Sachs disease, infantile type 2 sialidosis, Hurler's syndrome, and Sanfilippo's syndrome. There were large meganeurites on pyramidal neurons in Tay-Sachs disease, and small ones in Hurler's and Sanfilippo's syndromes...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(85)90078-0
更新日期:1985-06-01 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::This article reviews stem cell-based strategies for spinal cord injury repair, and practical issues concerning their translation to the clinic. Recent progress in the stem cell field includes clinically compliant culture conditions and directed differentiation of both embryonic stem cells and somatic stem cells. We pr...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1016/j.expneurol.2007.09.002
更新日期:2008-02-01 00:00:00
abstract::Three-day-old rats received an infusion of a small dose of 6-hydroxydopamine (6-OHDA) (12 micrograms) directly into the locus ceruleus nuclei, in order to induce a subtotal lesion of the noradrenergic system. Significant modifications in cerebellum maturation were observed, mainly a regression failure in the perisomat...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(85)90120-7
更新日期:1985-04-01 00:00:00
abstract::This study examined the effect of experimental diabetes on the anterograde and retrograde axonal transport of phosphofructokinase activity. Rats with streptozotocin-induced diabetes of 4 weeks duration showed phosphofructokinase activity accumulation deficits both proximal (53% and 65% in two separate experiments) and...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(87)90180-4
更新日期:1987-04-01 00:00:00
abstract::Cordotomy-denervation interactions were studied on contractile and myofibrillar properties of slow (soleus) and fast (extensor digitorum longus) muscles of the rat. The spinal cord was transected midthoracically in neonatal (2-day-old) animals. Two months after birth, a unilateral transection of the sciatic nerve was ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(88)90214-2
更新日期:1988-04-01 00:00:00
abstract::Cortical spreading depression (CSD) is associated with various short- and long-term physiological and neurochemical changes and has been shown to confer an increased susceptibility to accompanying ischemic injury or provide protection against a subsequent experimental ischemia. Nitric oxide is involved in the processe...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1999.7218
更新日期:1999-12-01 00:00:00
abstract::Calcium-independent nitric oxide synthase (NOS) activity has been reported in ischemic brains and usually attributed to the inducible isoform, iNOS. Because calcium-independent mechanisms have recently been shown to regulate the constitutive calcium-dependent NOS, we proposed to confirm the presence of iNOS activity i...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2005.05.001
更新日期:2005-09-01 00:00:00
abstract::Methylmalonic acidemia is an inherited metabolic disorder that leads to brain damage associated to the accumulation of methylmalonic acid (MMA) and impairment of energy metabolism. We demonstrate here that treatment with diazoxide, an agonist of mitochondrial ATP-sensitive K(+) channels (mitoK(ATP)), can prevent death...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2006.04.004
更新日期:2006-09-01 00:00:00
abstract::The Fmr1 knockout (KO) mouse is characterized by an increased audiogenic seizure (AGS) susceptibility and is considered a good animal model for epilepsy and seizures in the human fragile-X (FRAX) syndrome. Here, we tested the hypothesis that the reintroduction of the FMR1 gene is able to revert the AGS susceptibility ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2006.08.007
更新日期:2007-01-01 00:00:00
abstract::The present experiments focused on the morphological interaction between serotonergic (5-HT) and noradrenergic (NA) axons during regeneration following partial axonal denervation in the cerebral cortex in adult rats. The denervation paradigm used employed two neurotoxins, one for 5-HT and one for NA axons, infused tog...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/s0014-4886(03)00221-8
更新日期:2003-11-01 00:00:00
abstract::Previously injured dorsal roots were electrically stimulated to determine if regenerating sensory axons can form physiologically active synaptic contacts with neurons within fetal spinal cord tissue transplants. Dorsal rootlets, sectioned at their spinal cord entry zone, were apposed to intraspinal transplants of feta...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1996.0101
更新日期:1996-06-01 00:00:00
abstract::The hph-1 mice have defective tetrahydrobiopterin biosynthesis and share many neurochemical similarities with l-dopa-responsive dystonia (DRD) in humans. In both, there are deficiencies in GTP cyclohydrolase I and low brain levels of dopamine (DA). Striatal tyrosine hydroxylase (TH) levels are decreased while the numb...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2004.08.022
更新日期:2004-12-01 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
abstract::Peroxiredoxin-2 (PRX-2) is known to be released from erythrocytes and induce brain damage after intracerebral hemorrhage (ICH); lipocalin-2 (LCN-2) is involved in neuroinflammation following ICH. This study examined the role of LCN-2 in PRX-2 induced brain injury and involved three parts. In the first part, adult male...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2020.113521
更新日期:2021-01-01 00:00:00
abstract::Death-associated protein kinase 1 (DAPK1) is a key protein that mediates neuronal death in ischemic stroke. Although the substrates of DAPK1 and molecular signal in stroke have been gradually discovered, the modulation of DAPK1 itself is still unclear. Here we first reveal that Caytaxin, a brain-specific member of BCL...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2020.113303
更新日期:2020-07-01 00:00:00
abstract::Huntington's disease (HD) is an inherited progressive neurodegenerative disorder characterized by progressive movement, psychiatric and cognitive disturbances. Previous studies have indicated that HD pathogenesis may be mediated in part by loss of brain derived neurotrophic factor (BDNF). Antidepressants selectively b...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2007.10.015
更新日期:2008-03-01 00:00:00
abstract::Relatively few behavioral deficits are apparent in subjects with hereditary absence of the corpus callosum (CC). The anterior commissure (AC) has been suggested to provide an extracallosal route for the transfer of interhemispheric information in subjects with this congenital defect. Anterior commissure size, axon num...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6564
更新日期:1997-08-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) support axon regeneration across artificial nerve bridges but their differentiative capacity and ability to promote nerve regeneration remains unclear. In this study, MSCs isolated from bone marrow of Sprague-Dawley rats were characterized by plastic adherence and pluripotency towards mes...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2011.01.013
更新日期:2011-04-01 00:00:00
abstract::The majority of human spinal cord injuries involve gray matter loss from the cervical or lumbar enlargements. However, the deficits that arise from gray matter damage are largely masked by the severe deficits due to associated white matter damage. We have developed a model to examine gray matter-specific deficits and ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1999.7016
更新日期:1999-03-01 00:00:00
abstract::By way of commentary on a recent report that transplanted adult neural progenitor cells can alleviate functional deficits in a rat lesion model of Huntington's disease [Vazey, E.M., Chen, K., Hughes, S.M., Connor, B., 2006. Transplanted adult neural progenitor cells survive, differentiate and reduce motor function imp...
journal_title:Experimental neurology
pub_type: 评论,杂志文章,评审
doi:10.1016/j.expneurol.2006.11.007
更新日期:2007-02-01 00:00:00
abstract::The sub-thalamic nucleus (STN) is relevant to the preparation of movement ignition but its role in movement termination is uncertain. Fourteen patients with Parkinson's disease (PD) received local field potentials (LFPs) recording at the left STN on the fourth day after deep brain stimulation surgery. They performed p...
journal_title:Experimental neurology
pub_type: 临床试验,杂志文章
doi:10.1016/j.expneurol.2011.10.013
更新日期:2012-01-01 00:00:00
abstract::Injection of lysosomal enzyme into cisternal or ventricular cerebrospinal fluid (CSF) has been carried out in 11 lysosomal storage disorder models, with each study demonstrating reductions in primary substrate and secondary neuropathological changes, and several reports of improved neurological function. Whilst acute ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2014.09.008
更新日期:2015-01-01 00:00:00
abstract::Genetic and protein studies have indicated abnormalities in alpha-synuclein in neurodegenerative diseases. However, the developmental localization and cellular role of synuclein isoforms is contentious. We investigated the cellular localization of alpha-, beta-, and gamma-synuclein in developing cultured rat neurons a...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/s0014-4886(03)00108-0
更新日期:2003-07-01 00:00:00
abstract::We have investigated the formation of DNA adducts and oxidative base damage produced by copper sulfate activation of dopamine and 6-hydroxydopamine. In the presence of 10 microM copper sulfate both 100 microM dopamine and 100 microM 6-hydroxydopamine formed three similar DNA adducts with relative adduct levels of 8.36...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6560
更新日期:1997-08-01 00:00:00
abstract::The amount of myelination in vivo and in vitro depends on the number of oligodendrocyte progenitors, their differentiation, and on the neuron function. It has been shown that continuous administration of FGF2, a mitotic and neuroprotective factor, allows oligodendrocyte progenitors to proliferate, but prevents them fr...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/s0014-4886(02)00053-5
更新日期:2003-05-01 00:00:00
abstract::Alzheimer's disease (AD) is characterized by cognitive decline and deposition of beta-amyloid (Abeta) plaques in cortex and hippocampus. A transgenic mouse AD model (Tg2576) that overexpresses a mutant form of human Abeta precursor protein exhibits age-related cognitive deficits, Abeta plaque deposition, and oxidative...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/s0014-4886(03)00399-6
更新日期:2003-11-01 00:00:00
abstract::Despite the importance of the periaqueductal gray (PAG) in the modulation of nociception and pain, many aspects of the roles of the different columns of the PAG in descending controls: facilitation and inhibition, are not understood. Employing a tonic muscle pain model established by i.m. injection of 5.8% saline into...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2014.04.019
更新日期:2014-07-01 00:00:00
abstract::The role of capsaicin-sensitive afferents in neurogenic voiding dysfunction was studied in chronic spinal cord injured rats (SCI). Cystometry and external urethral sphincter (EUS) electromyography were performed on 2 consecutive days after induction of urethane anesthesia in SCI rats 6-8 weeks after spinal cord injury...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2004.02.014
更新日期:2004-06-01 00:00:00