Abstract：
:Major practical constraints on neural grafting in Parkinson's disease are the shortage of human donor tissue and the great loss of dopamine neurons during the grafting procedure. The vast majority of implanted embryonic dopamine neurons are believed to die within a few days of transplantation surgery, at least in part through apoptosis. We have previously found that survival of nigral grafts in rodents can be significantly augmented by pretreatment with the caspase inhibitor Ac-YVAD-cmk or by lazaroids (lipid peroxidation inhibitors). We now report that pretreatment with the caspase inhibitor Ac-DEVD-cmk, but not z-VAD-fmk, results in a significantly improved survival of transplanted dopamine neurons of similar magnitude to that achieved in this study using Ac-YVAD-cmk (both 220-230% of control). In addition, we found that treatment of the graft tissue with tirilazad mesylate (a lazaroid allowed for clinical use) almost doubled the survival of grafted dopamine neurons. When Ac-YVAD-cmk and tirilazad mesylate treatments were combined, the number of surviving dopamine neurons increased significantly further to 280% of control. Importantly, the same combination of neuroprotectants enhanced the survival of human dopamine neurons xenotransplanted to immunosuppressed rats (to 240% of control). In conclusion, these results suggest that combining treatments that counteract oxidative stress and caspase activation is a valuable strategy to enhance nigral graft survival that should be considered for clinical application.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Hansson O,Castilho RF,Kaminski Schierle GS,Karlsson J,Nicotera P,Leist M,Brundin Pdoi
10.1006/exnr.2000.7406keywords:
subject
Has Abstractpub_date
2000-07-01 00:00:00pages
102-11issue
1eissn
0014-4886issn
1090-2430pii
S0014-4886(00)97406-5journal_volume
164pub_type
杂志文章abstract：:The Alzheimer's disease-related peptide beta(1-40) amyloid self-associates to form fibrils exhibiting a morphology characteristic of amyloidogenic proteins. The mechanism of this fibrillization process has yet to be fully elucidated. In this study we have immobilized the beta(1-40) amyloid to flat gold surfaces using ...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1999.7114
更新日期：1999-08-01 00:00:00
abstract：:Impaired olfaction is an early symptom of Alzheimer disease (AD). This likely to reflect neurodegenerative processes taking place in basal telencephalic structures that mediate olfactory processing, including the anterior olfactory nucleus. Betaeta-amyloid (Abeta) accumulation in AD brain may relate to decline in soma...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2009.06.010
更新日期：2010-06-01 00:00:00
abstract：:One of the sexual dimorphic differences in adult rodents is neural proliferation. Here we demonstrate that physiological hormone stages can modulate this proliferation in the adult forebrain. Female mice, both pregnant and synchronized in oestrus, exhibited higher proliferating cell percentages than males in both the ...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2008.12.013
更新日期：2009-04-01 00:00:00
abstract：:Excitotoxic mechanisms may play a critical role in the pathophysiology of several neurological and psychiatric diseases. Excitatory amino acid receptor antagonists are therefore of great therapeutic interest, but untoward side effects often prevent their clinical use. Targeting the glycine coagonist site of the (NMDA)...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1999.7284
更新日期：2000-05-01 00:00:00
abstract：:Ca2+ influx through NMDA receptor-gated channels and the subsequent rise in intracellular Ca2+ concentration ([Ca2+]i) have been implicated in cytotoxic processes that lead to irreversible neuronal injury. While many studies have focused on cytosolic Ca2+ homeostasis, much less is known about Ca2+ fluxes in subcellula...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1997.6599
更新日期：1998-01-01 00:00:00
abstract：:Among endogenous adaptive systems to hypoxia, neuroglobin, a recently discovered heme protein, was suggested as a novel oxygen-dependent neuroprotectant. We aimed to characterize i) maturational age-related regulation of neuroglobin in the developing mouse brain under normoxic and hypoxic conditions, and ii) the role ...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2012.04.006
更新日期：2012-07-01 00:00:00
abstract：:The development of transgenic mouse models of amyotrophic lateral sclerosis (ALS) allows the testing of neuroprotective agents. We evaluated the effects of five agents in transgenic mice with the G93A Cu,Zn superoxide dismutase mutation. A novel inhibitor of poly(ADP-ribose) polymerase showed no effects on survival. D...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.2001.7633
更新日期：2001-04-01 00:00:00
abstract：:The role of interferon-gamma (IFN-gamma) in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) is still controversial. We have studied the function of IFN-gamma and its receptor in the EAE model using two different IFN-gamma receptor knockout (IFN-gamma R(-/-)) mouse types: C57B...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.2001.7815
更新日期：2001-12-01 00:00:00
abstract：:Electrophysiological studies on preganglionic neurons (PGNs) in the dorsal motor nucleus (DMN) of the vagus nerve has been hampered by technical limitations. Conventional electrical stimulation of the vagus nerve with cathodal square-wave pulses activates both preganglionic and afferent fibers. Thus, some PGNs cannot ...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(86)90076-2
更新日期：1986-02-01 00:00:00
abstract：:We have previously found that fetal cortex taken from 16- to 18-day-old donors survives grafting to the infarcted cortex 5-7 days after middle cerebral artery occlusion. The present study was undertaken to examine the effect on graft survival of varying the age of the fetal donor tissue and the time between vessel occ...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1994.1086
更新日期：1994-05-01 00:00:00
abstract：:Diffuse and neuritic plaques are sites of accumulation of beta-amyloid peptides (A beta) in the brains of Alzheimer's disease (AD) patients. Although amyloid fibrils are formed from A beta, the contribution of other plaque-associated proteins and peptides to the pathogenesis of AD amyloidosis is unknown. To pursue thi...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1994.1209
更新日期：1994-12-01 00:00:00
abstract：:Status epilepticus (SE) is an acute event, characterized by repeated or continuous seizures, which alters neuronal properties of the brain and can promote the epileptic disorder. Experimental observations indicate that SE becomes progressively less responsive to anti-epileptic drugs, suggesting changes in the underlyi...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2012.01.020
更新日期：2012-04-01 00:00:00
abstract：:Pompe disease is an inherited disorder due to a mutation in the gene that encodes acid α-glucosidase (GAA). Children with infantile-onset Pompe disease develop progressive hypotonic weakness and cardiopulmonary insufficiency that may eventually require mechanical ventilation (MV). Our team conducted a first in human t...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2016.07.013
更新日期：2017-01-01 00:00:00
abstract：:Neonatal hypoxia ischemia (HI) is the main cause of newborn mortality and morbidity. Preclinical studies have shown that the immature rat brain is more resilient to HI injury, suggesting innate mechanisms of neuroprotection. During neonatal period brain metabolism experience changes that might greatly affect the outco...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2020.113317
更新日期：2020-08-01 00:00:00
abstract：:Amphetamine derivatives are the most commonly abused drugs. These compounds have been known for many years to induce neurotoxicity. However, recent findings have highlighted novel alterations produced by amphetamines in the central nervous system consisting of neuronal inclusions and the involvement of proteins belong...
journal_title：Experimental neurology
pub_type： 杂志文章,评审
doi：10.1016/j.expneurol.2006.02.130
更新日期：2006-09-01 00:00:00
abstract：:We compared the magnetic cerebral activity of 10 fetal subjects at two different gestational ages. Spontaneous cerebral activity was recorded with a large array magnetometer specially designed to conform to the maternal gravid abdomen during the third trimester of pregnancy. We recorded each fetal subject at least twi...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2004.06.026
更新日期：2004-11-01 00:00:00
abstract：:In what ways do passive touch and active touch require particular properties of cortical physiology? Because it is not easy to make predictions "bottom up" from neurophysiology and anatomy to behavior, there have been surprises in studying behavioral deficits following selective ablations of SI versus SII. For example...
journal_title：Experimental neurology
pub_type： 杂志文章,评审
doi：10.1006/exnr.1994.1017
更新日期：1994-01-01 00:00:00
abstract：:Chondroitin sulfate proteoglycans (CSPGs) are extracellular matrix (ECM) molecules that are widely expressed throughout the developing and adult CNS. In vitro studies demonstrate their potential to restrict neurite outgrowth, and it is believed that CSPGs also inhibit axonal regeneration after CNS injury in vivo. Prev...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/s0014-4886(03)00087-6
更新日期：2003-08-01 00:00:00
abstract：:Volume-regulated anion channels (VRACs) are critically involved in regulating cell volume, and leucine-rich repeat-containing protein 8A (LRRC8A, SWELL1) is an obligatory subunit of VRACs. Cell swelling occurs early after brain ischemia, but it is unclear whether neuronal LRRC8a contributes to ischemia-induced glutama...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2020.113391
更新日期：2020-10-01 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：:Motor nerve conduction velocity was measured in six branches of the sciatic nerve in streptozotocin-diabetic rats. It was markedly reduced in nerves to the gastrocnemius, soleus, tibialis anterior, and extensor digitorum longus muscles. The branch to the plantaris muscle remained unaffected. In control rats none of th...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(86)90315-8
更新日期：1986-06-01 00:00:00
abstract：:Ghrelin has been shown to regulate neurogenesis in the hippocampus. The aim of this study was to investigate the possible influence of ghrelin on cell proliferation and neuroblast formation in the subventricular zone (SVZ) and rostral migratory system (RMS) and generation of interneurons in the olfactory bulb (OB). We...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2013.11.021
更新日期：2014-02-01 00:00:00
abstract：:Estrogen has been suggested to be pro-epileptic by reducing GABA synthesis, resulting in increased spine density and a decreased threshold for seizures in the hippocampus, which, once they occur, are characterized by a dramatic spine loss in the affected brain areas. As considerable amounts of estradiol are synthesize...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2006.07.020
更新日期：2007-01-01 00:00:00
abstract：:Parkinson's disease (PD) is characterized by the polymerization of wild-type (WT) or mutant alpha-synuclein (AS) into aggregates and fibrils, which are observed as Lewy bodies (LBs) and Lewy neurites (LNs) in PD patients. However, inability to demonstrate aggregation in many cell culture systems is a major drawback fo...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2005.10.019
更新日期：2006-02-01 00:00:00
abstract：:Injections of horseradish peroxidase were made into surgically exposed superior cervical ganglia of Sprague-Dawley rats weighing 250 to 320 g. Anterogradely labeled postganglionic fibers were observed in the nervus conarii, pineal gland, pineal stalk, and the choroid plexus. Terminal fields were identified in lamina i...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(87)90101-4
更新日期：1987-08-01 00:00:00
abstract：:Given the prevalence and societal impact of autism spectrum disorders (ASD), there is an urgent need to develop innovative preventative strategies and treatments to reduce the alarming number of cases and improve core symptoms for afflicted individuals. Translational efforts between clinical and preclinical research a...
journal_title：Experimental neurology
pub_type： 杂志文章,评审
doi：10.1016/j.expneurol.2017.07.021
更新日期：2018-01-01 00:00:00
abstract：:Chondroitin sulfate proteoglycans (CSPGs), extracellular matrix molecules that increase dramatically following a variety of CNS injuries or diseases, have long been known for their potent capacity to curtail cell migrations as well as axon regeneration and sprouting. The inhibition can be conferred through binding to ...
journal_title：Experimental neurology
pub_type： 杂志文章,评审
doi：10.1016/j.expneurol.2020.113276
更新日期：2020-06-01 00:00:00
abstract：:Glomerular convergence has been proposed to rely on interactions between like olfactory axons, however topographic targeting is influenced by guidance molecules encountered in the olfactory bulb. Disruption of these cues during development misdirects sensory axons, however little is known about the role of bulb-derive...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2007.06.022
更新日期：2007-10-01 00:00:00
abstract：:Estimates were made of the changing volumes of discharge arising from the total populations of Ia and II spindle afferent fibers in the cat's deefferented medial gastrocnemius as the muscle was extended stepwise over its excursion range. The estimates were based on values reported elsewhere for (i) the incidence of ac...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(83)90017-1
更新日期：1983-04-01 00:00:00
abstract：:The effect of sinusoidal magnetic field stimulation on regeneration of the rat sciatic nerve was studied. Rats were exposed, after crush lesioning of the nerve, between a pair of Helmholtz coils to a 50 Hz magnetic field of 0.2 mT or 0.4 mT, respectively. Regeneration of the sciatic nerve was measured by the "pinch te...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(91)90132-v
更新日期：1991-06-01 00:00:00
