Enriched environment and astrocytes in central nervous system regeneration

University of Gothenburg, Goeteborg, Västra Götaland, Sweden
Journal of Rehabilitation Medicine (Impact Factor: 1.68). 06/2007; 39(5):345-52. DOI: 10.2340/16501977-0084
Source: PubMed


Rehabilitation medicine is entering a new era, based on the knowledge that the central nervous system has a substantial capacity for repair and regeneration. This capacity is used in 3 distinct but overlapping situations: (i) routine housekeeping throughout life (i.e. taking care of normal wear-and-tear); (ii) older age, when functional reserves of various kinds are depleted, resulting in cognitive, motor, and other deficits; and (iii) contexts in which a neurological deficit reflects an acute or chronic pathological process, such as neurotrauma, stroke, or neurodegenerative disease. The positive message here is two-fold. First, some aspects of regeneration occur even in the adult and ageing brain and spinal cord, and we are starting to unravel the underlying molecular mechanisms. Secondly, novel therapeutic approaches and targets are emerging that will substantially increase the efficiency and efficacy of rehabilitation and will transform rehabilitation into a discipline focusing both on its traditional domain and on prevention, ultimately across all the age categories. This review attempts to sum up the present knowledge about an enriched environment, currently the single most efficient plasticity- and regeneration-promoting paradigm. It also summarizes research showing that astrocytes - considered only years ago merely to nurse and support neurones - are a novel and highly interesting target for regenerative strategies in the brain and spinal cord.

    • "estradiol and testosterone during the development of hippocampus of rats (Conejo et al., 2005). The development of astrocyte processes increases the GFAP positive reaction in astrocytes of hippocampal sections in an in vitro environment (Del Cerro et al., 1995) and modifies the astrocyte response after the brain injury (Nilsson and Pekny, 2007). Moreover, the astrocyte processes density and GFAP positive reactions in hippocampus of rats fluctuates during the different estrous cycles and increases in proestrus phase when gonadal hormones are at their highest level (Struble et al., 2006). "
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    ABSTRACT: The aging process affects all body tissues including the brain and different hormones are reduced with aging in mammals. This research was performed to study the effects of 17β-estradiol on astrocyte density in CA1 region of hippocampus during the aging process. Female Wistar rats were divided into the following five groups: immature rats, mature rats in metestrus phase, mature rats treated with 17β-estradiol, old rats in metestrus phase and old rats treated with 17β-estradiol. The groups received 50 μg/kg 17β-estradiol subcutaneously daily injections for a period of 7 days. The groups in metestrus phase were detected on the basis of observed cells in the vaginal smear. The results revealed increased astrocyte density in groups possessing a better condition in estradiol hormone. INTRODUCTION Astrocytes are a sub-type of glial cells in the central nervous system. They are star-shaped with many processes envelope synapses made by neurons (Venkatesh et al., 2013). Astrocytes perform many functions, including biochemical support of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, and a role in the repair and scarring process of the brain. During the embryogenesis, glial cells direct the neuronal migration along with production of molecules that modify the axons and dendrites growth (Allen and Barres, 2005). Recent studies indicate that glial cells in the hippocampus and cerebellum participate in synaptic transmission, regulation of neurotransmitters distance from the synaptic cleft, release of factors including ATP that regulates pre-synaptic function and even release of neurotransmitters. Moreover, unlike neurons, glial cells are capable of mitotic division (Kuffler and Nicholls, 2000). Astrocytes are believed to be the most abundant type of glial cells that outnumber neurons with a proportion of 10 to 1 and having occupied 25 to 50 percent of the brain volume. Astrocytes are formed like continuous bricks throughout CNS with no overlay (Fiacco et al., 2008). Astrocytes are broadly divided into two groups: protoplasmic astrocytes found in the brain's grey matter and fibrous astrocytes of the white matter. Protoplasmic astrocytes are intimately associated with neuronal cell bodies and synapses, whereas fibrous astrocytes are associated with neuronal axons (Allen and Barres, 2009). Gonadal hormones participate in regulation of hippocampal morphology and activity using their influence on both neural and glial cells specially astrocytes (Hajszan et al., 2007; Reyna-Neyra et al., 2002; Tanapat et al., 2005). Astrocytes possess perivascular feet covering around 85 percent of the surface of capillaries in the CNS (Sofroniew and Vinters, 2010). These cells possess a bunch of 9-nm-itermediate filaments that are made of Glial fibrillary acidic protein (GFAP) that strengthens their structure. GFAP is the marker of astrocytes identification (Isaacs et al., 1998). GFAP is an intermediate filament (IF) protein that is expressed by numerous cell types of the central nervous system including astrocytes (Jacque et al., 1978), and ependymal cells (Roessmann et al., 1980). The agrin expression, a protein derived from astrocytes involving in formation of synapses is induced by progesterone (Tournell et al., 2006) while estradiol influences astrocytes and enhances neurite outgrowth by repressing GFAP expression and reorganizing laminin (Rozovsky et al., 2002). Estradiol regulates the GFAP expression in hypothalamus and hippocampus of the rat in both in vivo and in vitro (Stone et al., 1998). Astrocytes number is regulated by
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    • "The lack or inadequacy of endogenous neuronal replacement after brain lesions encouraged investigations on the role of glial cells in poststroke recovery process. Increasing evidence indicate that glial cells crucially contribute to the degenerative and regenerative processes following ischemic brain lesions [184, 185]. Also, some of the beneficial effects of EE on the postischemic brain might be mediated by a dynamic modulation of different glial populations. "
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    ABSTRACT: Stroke is a common and disabling global health-care problem, which is the third most common cause of death and one of the main causes of acquired adult disability in many countries. Rehabilitation interventions are a major component of patient care. In the last few years, brain stimulation, mirror therapy, action observation, or mental practice with motor imagery has emerged as interesting options as add-on interventions to standard physical therapies. The neural bases for poststroke recovery rely on the concept of plasticity, namely, the ability of central nervous system cells to modify their structure and function in response to external stimuli. In this review, we will discuss recent noninvasive strategies employed to enhance functional recovery in stroke patients and we will provide an overview of neural plastic events associated with rehabilitation in preclinical models of stroke.
    Full-text · Article · Jun 2013 · Neural Plasticity
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    • "The human primary motor cortex (M1) has a great reorganization ability in adults following repetitions of simple movement and motor skill training (Karni et al. 1995; Pascual-Leone et al. 1995; Classen et al. 1998), environmental change (Muellbacher et al. 2000; Nilsson & Pekny, 2007) and injury to the sensorimotor system (Brasil-Neto et al. 1993; Chen et al. 2002; Nudo, 2003; Rossini et al. 2007). This maintained plasticity helps us to adjust to various external and internal conditions. "
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    ABSTRACT: Paired associative stimulation (PAS) is an effective non-invasive method to induce human motor plasticity by the repetitive pairing of peripheral nerve stimulation and transcranial magnetic stimulation (TMS) at the primary motor cortex (M1) with a specific time interval. Although the repetitive pairing of two types of afferent stimulation might be a biological basis of neural plasticity and memory, other types of paired stimulation of the human brain have rarely been studied. We hypothesized that the repetitive pairing of TMS and interhemispheric cortico-cortical projection or paired bihemispheric stimulation (PBS), in which the right and left M1 were serially stimulated with a time interval of 15 ms, would produce an associative long-term potentiation (LTP)-like effect. In this study, 23 right-handed healthy volunteers were subjected to a 0.1 Hz repetition of 180 pairings of bihemispheric TMS, and physiological and behavioural measures of the motor system were compared before, immediately after, 20 min after and 40 min after PBS intervention. The amplitude of the motor evoked potential (MEP) induced by the left M1 stimulation and its input-output function increased for up to approximately 20 min post-PBS. Fine finger movements were also facilitated by PBS. Spinal excitability measured by the H-reflex was insensitive to PBS, suggesting a cortical mechanism. The associative LTP-like effect induced by PBS was timing dependent, occurring only when the interstimulus interval was 5-25 ms. These findings demonstrate that using PBS in PAS can induce motor cortical plasticity, and this approach might be applicable to the rehabilitation of patients with motor disorders.
    Full-text · Article · Sep 2009 · The Journal of Physiology
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