Combining enriched environment and induced pluripotent stem cell therapy results in improved cognitive and motor function following traumatic brain injury.

Abstract:

PURPOSE:Despite advances towards potential clinically viable therapies there has been only limited success in improving functional recovery following traumatic brain injury (TBI). In rats, exposure to an enriched environment (EE) improves learning and fosters motor skill development. Induced pluripotent stem cells (iPSC) have been shown to survive transplantation and influence the recovery process. The current study evaluated EE and iPSC as a polytherapy for remediating cognitive deficits following medial frontal cortex (mFC) controlled cortical impact (CCI) injury. METHODS:Sixty adult male rats received a midline mFC CCI or sham injury and were randomly placed in either EE or standard environment (SE). Seven days post-injury rats received bilateral transplantation of iPSCs or media. Behavioral measures were conducted throughout the remainder of the study. Following behavioral analysis, brains were extracted and prepared for histological analysis. RESULTS:Open-field data revealed that combined therapy resulted in typical Sham/EE activity rearing patterns by the conclusion of the study. On the Vermicelli Handling task, rats with EE/iPSC polytherapy performed better than media-treated rats. Furthermore, rats treated with polytherapy performed equivalently to Sham/EE rats on the Morris water maze. Proficiency on the Rotarod was consistently better in EE when compared to SE counterparts. Confocal microscopy confirmed that iPSCs survived and migrated away from the transplantation site. CONCLUSIONS:Overall, EE or iPSC therapy improved cognition and motor performance, however, full cognitive restoration was seen only with the EE/iPSC treatment. These data suggest that EE/iPSC therapy should be explored as a potential, clinically relevant, treatment for TBI.

journal_name

Restor Neurol Neurosci

authors

Dunkerson J,Moritz KE,Young J,Pionk T,Fink K,Rossignol J,Dunbar G,Smith JS

doi

10.3233/RNN-140408

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

675-87

issue

5

eissn

0922-6028

issn

1878-3627

pii

9433263611667555

journal_volume

32

pub_type

杂志文章
  • Suprachiasmatic nucleus lesions abolish and fetal grafts restore circadian gnawing rhythms in hamsters.

    abstract::It is widely accepted that the suprachiasmatic nuclei (SCN) of the hypothalamus serve as biological pacemakers, organizing daily activities. However some circadian rhythms are controlled by extra-SCN structures. Transplantation of fetal donor SCN in SCN-lesioned rodents induces recovery of rhythmic locomotor and drink...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-1994-6207

    authors: Le Sauter J,Silver R

    更新日期:1994-01-01 00:00:00

  • Training ameliorates deficits in visual detection and orienting following lesions of primary visual cortex sustained in adulthood and in infancy.

    abstract::Purpose: Damage of primary visual cortex in adult humans, monkeys and cats severely disrupts vision by disconnecting much of the cogni-tive processing machinery of extrastriate cortex from its source of visual signals in the retina. Equivalent lesions sustained early in life result in partial sparing of visual process...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:

    authors: Payne BR,Lomber SG

    更新日期:2000-01-01 00:00:00

  • The development of emotion perception in face and voice during infancy.

    abstract:PURPOSE:Interacting with others by reading their emotional expressions is an essential social skill in humans. How this ability develops during infancy and what brain processes underpin infants' perception of emotion in different modalities are the questions dealt with in this paper. METHODS:Literature review. RESULT...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章,评审

    doi:10.3233/RNN-2010-0499

    authors: Grossmann T

    更新日期:2010-01-01 00:00:00

  • The difference between mechanisms of kainate and glutamate excitotoxicity in vitro: osmotic lesion versus mitochondrial depolarization.

    abstract::The hypothesis that a destabilization of mitochondrial function during neuronal exposure to excitatory amino acids may be involved in the mechanism of neuronal death was examined. The mitochondrial membrane potential (Delta(psi)m) and the cytoplasmic Ca2+ concentration ([Ca2+]c) were monitored simultaneously in single...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:

    authors: Kiedrowski L

    更新日期:1998-06-01 00:00:00

  • Modulation of cortical and spinal inhibition with functional recovery of upper extremity motor function among patients with chronic stroke.

    abstract:PURPOSE:We hypothesized that recovery of upper extremity motor function is associated with reduction of intracortical inhibition and improved reciprocal inhibition. This study examines the relationships of functional recovery in chronic stroke with the intracortical inhibition and spinal reciprocal inhibition. METHODS...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-150547

    authors: Fujiwara T,Honaga K,Kawakami M,Nishimoto A,Abe K,Mizuno K,Kodama M,Masakado Y,Tsuji T,Liu M

    更新日期:2015-01-01 00:00:00

  • Fetal porcine ventral mesencephalon grafts: dissection procedure and cellular characterization in culture.

    abstract::The objective of this study was to develop an optimal dissection procedure for fetal porcine ventral mesencephalon (VM) grafts and to characterize the cellular composition of such an explant, in particular with respect to the dopaminergic and GABAergic components. We have used a monolayer cell culture system to study ...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-1994-7402

    authors: van Roon WM,Copray JC,Hogenesch RI,Kema I,Meyer EM,Molenaar G,Lugard C,Staal MJ,Go KG

    更新日期:1995-01-01 00:00:00

  • Allogenic umbilical cord blood therapy combined with erythropoietin for patients with severe traumatic brain injury: three case reports.

    abstract:OBJECTIVE:To report the safety and efficacy of a novel therapeutic trial with umbilical cord blood (UCB) and concomitant recombinant human erythropoietin (rhEPO), which was tried for three cases of severe traumatic brain injury (TBI) in rehabilitation. DESIGN:Case series. SETTING:University hospital setting. PARTICI...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-120289

    authors: Min K,Song J,Lee JH,Kang MS,Jang SJ,Kim SH,Kim M

    更新日期:2013-01-01 00:00:00

  • Biochemical and anatomical analysis of cholinergic, noradrenergic and serotonergic innervation of fetal neocortical transplants placed in excitotoxin-induced neocortical lesions of adult rats.

    abstract::Fetal neocortical block transplants were implanted into the excitotoxically ablated sensorimotor cortex of adult rats in order to examine the density of innervation and distribution of presumptive host derived afferent fibers within these transplants. Cholinergic fiber innervation was examined at 3 months post graftin...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-1994-7301

    authors: Schulz MK,McNulty JA,Hogan TP,Zimmer J,Castro AJ

    更新日期:1995-01-01 00:00:00

  • Asymmetrical behavior in rats following striatal lesions and fetal transplants: the elevated body swing test.

    abstract::Animals with unilateral neurotoxic lesions in the striatum exhibit a stereotypical biased rotational behavior in response to dopamine agonists. We recently argued that the rotational test may be subject to sensitization effects of the drug. Accordingly, we proposed the drug-free elevated body swing test (EBST) as an a...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-1995-9103

    authors: Borlongan CV,Cahill DW,Sanberg PR

    更新日期:1995-01-01 00:00:00

  • Assessment of systemic administration of PEGylated IGF-1 in a mouse model of traumatic brain injury.

    abstract:BACKGROUND:Traumatic brain injury can result in lasting cognitive dysfunction due to degeneration of mature hippocampal neurons as well as the loss of immature neurons within the dentate gyrus. While endogenous neurogenesis affords a partial recovery of the immature neuron population, hippocampal neurogenesis may be en...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-180831

    authors: Sama DM,Carlson SW,Joseph B,Saenger S,Metzger F,Saatman KE

    更新日期:2018-01-01 00:00:00

  • Danhong injection facilitates recovery of post-stroke motion deficit via Parkin-enhanced mitochondrial function.

    abstract:BACKGROUND:A cerebral ischemic stroke involves mitochondrial dysfunction, motor deficits, and paralysis; and Danhong injection (DHI) might possess mitochondrial protection and functional recovery in a stroke subject through promoting expression of parkin, a ubiquitin ligase playing a key role in the regulation of prote...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-180828

    authors: Orgah JO,Ren J,Liu X,Orgah EA,Gao XM,Zhu Y

    更新日期:2019-01-01 00:00:00

  • Assessment of auditory temporal-order thresholds - a comparison of different measurement procedures and the influences of age and gender.

    abstract:PURPOSE:The relationship between auditory temporal-order perception and phoneme discrimination has been discussed for several years, based on findings, showing that patients with cerebral damage in the left hemisphere and aphasia, as well as children with specific language impairments, show deficits in temporal-process...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:

    authors: Fink M,Churan J,Wittmann M

    更新日期:2005-01-01 00:00:00

  • Reducing the rate of misdiagnosis in patients with chronic disorders of consciousness: Is there a place for audiovisual stimulation?

    abstract:BACKGROUND:The patients with chronic Disorders of Consciousness (DoC) mostly present with extremely challenging differential diagnosis. The advanced analysis of electroencephalographic (EEG) signals induced by brain stimulation paradigms may provide an appropriate approach to differentiate patients with DoC, besides th...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-170741

    authors: Naro A,Leo A,Bruno R,Cannavò A,Buda A,Manuli A,Bramanti A,Bramanti P,Calabrò RS

    更新日期:2017-01-01 00:00:00

  • Self-powered robots to reduce motor slacking during upper-extremity rehabilitation: a proof of concept study.

    abstract:BACKGROUND:Robotic rehabilitation is a highly promising approach to recover lost functions after stroke or other neurological disorders. Unfortunately, robotic rehabilitation currently suffers from "motor slacking", a phenomenon in which the human motor system reduces muscle activation levels and movement excursions, o...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-180830

    authors: Washabaugh EP,Treadway E,Gillespie RB,Remy CD,Krishnan C

    更新日期:2018-01-01 00:00:00

  • Modulation of motor function and cortical plasticity in health and disease.

    abstract::Basic science studies demonstrated mechanisms of plasticity and metaplasticity. More recent human studies identified some of these mechanisms as operating in multiple areas of human cognition, such as learning and memory, and in functional recovery from lesions in the CNS, as in stroke. One of the goals of neurorehabi...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章,评审

    doi:

    authors: Celnik PA,Cohen LG

    更新日期:2004-01-01 00:00:00

  • The Effect of Methylprednisolone on Caspase-3 Activation after Rat Spinal Cord Transection.

    abstract::Purpose: Caspase-3 is known as a crucial effector for apoptotic cell death. Apoptosis has recently been recognized as an important cell death mechanism after spinal cord injury (SCI). This study attempts to define the effect of methylprednisolone (MP) on the activation of caspase-3 in the lesioned area following SCI. ...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:

    authors: Li X,Oudega M,Dancausse HA,Levi AD

    更新日期:2000-01-01 00:00:00

  • Brain control of functional reach in healthy adults and stroke survivors.

    abstract:PURPOSE:Recovery of the most basic shoulder-flexion/elbow-extension components of functional reach is critical for effective arm function following stroke. In order to understand the mechanisms of motor recovery, it is important to characterize the pattern of brain activation during the reach task. METHODS:We evaluate...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-130361

    authors: Daly JJ,Hrovat K,Holcomb J,Pundik S

    更新日期:2014-01-01 00:00:00

  • Neuroprotective effects of bacopaside I in ischemic brain injury.

    abstract:PURPOSE:Bacopa monnieri (L.) WETTST. is extensively used in traditional Indian medicine as a nerve tonic. The neuropharmacological properties of bacopaside I, an important component from B. monnieri, have not been studied so far. The present study investigated the effects and possible mechanisms of bacopaside I in a ra...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-120228

    authors: Liu X,Yue R,Zhang J,Shan L,Wang R,Zhang W

    更新日期:2013-01-01 00:00:00

  • Increase in protein and tubulin mRNA synthesis in frog sensory neurons treated with the adenylate cyclase activator, forskolin.

    abstract::We are interested in the role cyclic AMP may play as a mediator of growth factor-induced gene expression in regenerating peripheral nerves. As a first step, we investigated mRNA levels and protein synthesis in intact frog dorsal root ganglia (DRG) treated with the adenylate cyclase activator, forskolin in vitro. Forsk...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-1990-13408

    authors: Carlsen RC,De Leon M,Tetzlaff W,Parhad IM,Bisby MA

    更新日期:1990-01-01 00:00:00

  • Developmental and reactive growth of dentate gyrus afferents: cellular and molecular interactions.

    abstract::The lamination of dentate gyrus afferents established during development is maintained following lesion-induced reactive growth in the adult. After partial deafferentation sprouts from undamaged afferents restore most synapses, while respecting the laminae relative boundaries. No evidence of trans-laminar sprouting ha...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章,评审

    doi:

    authors: Collazos-Castro JE,Nieto-Sampedro M

    更新日期:2001-01-01 00:00:00

  • Factors affecting septal graft amelioration of differential reinforcement of low rates (DRL) and activity deficits after fimbria-fornix lesions.

    abstract::Wound-derived trophic factors released by the injured brain are thought to reach a peak 1-2 weeks after injury. It has been proposed that such factors can promote the survival, growth and functional capacity of embryonic tissue grafts. To test the generality of this hypothesis, control rats and rats with aspirative fi...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-1989-1109

    authors: Dunnett SB,Martel FL,Rogers DC,Finger S

    更新日期:1989-01-01 00:00:00

  • Morphology of embryonic hippocampus transplants and generation of long-distance extrinsic graft fiber connections to the lateral septum and the entorhinal cortex in the mature rat brain.

    abstract::Pyramidal neurons inside transplants of embryonic nervous tissue are capable of generating axonal extrinsic hippocampal fiber connections over considerable distances to appropriate target areas in the mature brain. The establishment of long-distance graft efferents to the lateral septum and to the entorhinal cortex wa...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-1991-3103

    authors: Sprick U

    更新日期:1991-01-01 00:00:00

  • New perspectives in neurotrauma research.

    abstract::Traumatic brain and spinal cord injuries are severe burdens for the patients, their relatives, the health care providers and society as a whole. Recent data demonstrate the magnitude of the problem: It is mostly a disease of the young gen-eration (age 20-45 years) with mortality rates for severe traumatic brain injury...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:

    authors: Neugebauer E,Lefering R,Noth J

    更新日期:1999-01-01 00:00:00

  • Transient improvement of amphetamine-induced rotational behavior by PC12 cell grafts: studies with microdialysis.

    abstract::The effects of striatal transplantation of PC12 cells on amphetamine-induced rotational behavior and monoamine levels were examined in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions in the nigrostriatal pathway. A total of 9 × 104 or 9 × 105 cells of PC12 was implanted into 3 sites in the striatum and changes...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-1993-6105

    authors: Hori Y,Kageyama H,Kihara T,Ikeda M,Nakano A,Kurosawa A

    更新日期:1993-01-01 00:00:00

  • Comparison of hemodynamic changes after repetitive transcranial magnetic stimulation over the anatomical hand knob and hand motor hotspot: A functional near-infrared spectroscopy study.

    abstract:BACKGROUND:Low-frequency rTMS can induce upregulation of excitability in the contralateral hemisphere by interhemispheric interaction. OBJECTIVE:The aim of this study was to compare the effects of interhemispheric modulation on hemodynamic changes after applying low-frequency rTMS over the anatomical hand knob (HK) an...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-201032

    authors: Kim J,Kim H,Lee J,Lee HJ,Na Y,Chang WH,Kim YH

    更新日期:2020-01-01 00:00:00

  • Twist and turn into chronic disorders of consciousness: Potential role of the auditory stapedial reflex.

    abstract:BACKGROUND:Patients suffering from chronic disorders of consciousness (DOC), including minimally conscious state (MCS) and unresponsive wakefulness syndrome (UWS), typically show an awareness impairment paralleled by a significant reflex hyper-excitability, which depend on the cortical deafferentation following brain-d...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-160655

    authors: Naro A,Bruno R,Leo A,Russo M,Salviera C,Bramanti A,Bramanti P,Calabrò RS

    更新日期:2017-01-01 00:00:00

  • Ensheathing cells: Large scale purification from adult olfactory bulb, freeze-preservation and migration of transplanted cells in adult brain.

    abstract::Regenerating nerve fiber sprouts enveloped by olfactory bulb (OB) ensheathing cells (ECs) seem to escape the inhibitory influence of gliotic tissue. Accordingly, these cells may be useful for general repair of injured CNS. Relatively large numbers of ECs could be purified from confluent cultures of adult rat olfactory...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-1996-10104

    authors: Gudiño-Cabrera G,Nieto-Sampedro M

    更新日期:1996-01-01 00:00:00

  • rTMS with motor training modulates cortico-basal ganglia-thalamocortical circuits in stroke patients.

    abstract:BACKGROUND AND PURPOSE:Repetitive transcranial magnetic stimulation (rTMS) may enhance plastic changes in the human cortex and modulation of behavior. However, the underlying neural mechanisms have not been sufficiently investigated. We examined the clinical effects and neural correlates of high-frequency rTMS coupled ...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章,随机对照试验

    doi:10.3233/RNN-2012-110162

    authors: Chang WH,Kim YH,Yoo WK,Goo KH,Park CH,Kim ST,Pascual-Leone A

    更新日期:2012-01-01 00:00:00

  • Single-session tDCS-supported retraining does not improve fine motor control in musician's dystonia.

    abstract:BACKGROUND:Focal dystonia in musicians (MD) is a task-specific movement disorder with a loss of voluntary motor control during instrumental playing. Defective inhibition on different levels of the central nervous system is involved in the pathophysiology. Sensorimotor retraining is a therapeutic approach to MD and aims...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章,随机对照试验

    doi:10.3233/RNN-2011-0582

    authors: Buttkus F,Baur V,Jabusch HC,de la Cruz Gomez-Pellin M,Paulus W,Nitsche MA,Altenmüller E

    更新日期:2011-01-01 00:00:00

  • An experimental study of nerve grafting combined with silicone tubes in the rat model: Functional outcome and specificity of muscle reinnervation.

    abstract::Bridging large defects in mixed nerves is still an unsolved problem in reconstructive microsurgery. Two main aspects may be distinguished: one is to obtain an appropriate substitute for the lost neural tissue, the second to direct fibers toward their previous end-organs with the highest possible specificity. In the pr...

    journal_title:Restorative neurology and neuroscience

    pub_type: 杂志文章

    doi:10.3233/RNN-1997-11306

    authors: Papaloïzos MY,Holmquist B,Lundborg G

    更新日期:1997-01-01 00:00:00