Transplantation of cultured astrocytes attenuates degenerative changes in rats with kainic acid-induced brain damage

Ермакова, И. В.; Loseva, E. V.; Hodges, Helen; Sinden, John D.

doi:10.1007/s10517-006-0052-0

Cited by 5 publications

(6 citation statements)

References 13 publications

(16 reference statements)

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“…Therefore, the territories of loss of astrocyte support correlated with the neuron-damaged area in both NMDA- and KA-injected cortexes (Figs. 1 and 3), indicating that reactive astrocytes protect neurons in the injured brain as previously reported in several brain injury models (Ermakova et al, 2005; Haj-Yasein et al, 2012; Myer et al, 2006; Rothstein et al, 1992; 1995; Shi et al, 2012; Zeng et al, 2012). …”

Section: Discussionsupporting

confidence: 72%

“…A loss of EAAT2/GLT-1 and decreased glutamate transport have been identified in human ALS patients (Rothstein et al, 1992; 1995). In addition, astrocyte functional loss precedes neuronal death in spinal cord injury (Min et al, 2012), and transplantation of human astrocytes facilitates functional recovery after the injury (Ermakova et al, 2005; Myer et al, 2006). In the previous study, we showed that in ATP-injected brain, astrogliosis occurs and delayed neuronal death is absent (Jeong et al, 2013c).…”

Section: Discussionmentioning

confidence: 99%

“…Astrocytes also provide neurons with glucose and neurotrophic factors, and protect neurons from oxidative stress (Badaut et al, 2002; Chih and Roberts Jr, 2003; Raps et al, 1989; Tsacopoulos and Magistretti, 1996). It has been reported that selective ablation of reactive astrocytes exacerbates traumatic neuronal damage, and that transplantation of astrocytes diminishes brain damage (Ermakova et al, 2005; Myer et al, 2006). Loss of EAAT2/GLT-1 has been found in human amyotrophic lateral sclerosis (ALS) (Rothstein, 1995; Rothstein et al, 1992), and brain damage due to ischemia is aggravated in AQP4-deficient mice (Haj-Yasein et al, 2012; Shi et al, 2012; Zeng et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Astrogliosis Is a Possible Player in Preventing Delayed Neuronal Death

Jeong¹,

Ji²,

Min³

et al. 2014

Molecules and Cells

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Mitigating secondary delayed neuronal injury has been a therapeutic strategy for minimizing neurological symptoms after several types of brain injury. Interestingly, secondary neuronal loss appeared to be closely related to functional loss and/or death of astrocytes. In the brain damage induced by agonists of two glutamate receptors, N-ethyl-D-aspartic acid (NMDA) and kainic acid (KA), NMDA induced neuronal death within 3 h, but did not increase further thereafter. However, in the KA-injected brain, neuronal death was not obviously detectable even at injection sites at 3 h, but extensively increased to encompass the entire hemisphere at 7 days. Brain inflammation, a possible cause of secondary neuronal damage, showed little differences between the two models. Importantly, however, astrocyte behavior was completely different. In the NMDA-injected cortex, the loss of glial fibrillary acidic protein-expressing (GFAP+) astrocytes was confined to the injection site until 7 days after the injection, and astrocytes around the damage sites showed extensive gliosis and appeared to isolate the damage sites. In contrast, in the KA-injected brain, GFAP+ astrocytes, like neurons, slowly, but progressively, disappeared across the entire hemisphere. Other markers of astrocytes, including S100β, glutamate transporter EAAT2, the potassium channel Kir4.1 and glutamine synthase, showed patterns similar to that of GFAP in both NMDA- and KA-injected cortexes. More importantly, astrocyte disappearance and/or functional loss preceded neuronal death in the KA-injected brain. Taken together, these results suggest that loss of astrocyte support to neurons may be a critical cause of delayed neuronal death in the injured brain.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Astrogliosis Is a Possible Player in Preventing Delayed Neuronal Death

Jeong¹,

Ji²,

Min³

et al. 2014

Molecules and Cells

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“…Therefore, neurons can not live without support of astrocytes. Accordingly, it has been reported that selective ablation of reactive astrocytes exacerbates traumatic neuronal damage and that transplantation of astrocytes diminishes brain damage [18, 19]. We also found spatial-temporal correlation between delayed neuronal death and functional loss and/or death of astrocyte in the spinal cord injury [2].…”

Section: Introductionsupporting

confidence: 68%

Absence of Delayed Neuronal Death in ATP-Injected Brain: Possible Roles of Astrogliosis

2013

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Although secondary delayed neuronal death has been considered as a therapeutic target to minimize brain damage induced by several injuries, delayed neuronal death does not occur always. In this study, we investigated possible mechanisms that prevent delayed neuronal death in the ATP-injected substantia nigra (SN) and cortex, where delayed neuronal death does not occur. In both the SN and cortex, ATP rapidly induced death of the neurons and astrocytes in the injection core area within 3 h, and the astrocytes in the penumbra region became hypertropic and rapidly surrounded the damaged areas. It was observed that the neurons survived for up to 1-3 months in the area where the astrocytes became hypertropic. The damaged areas of astrocytes gradually reduced at 3 days, 7 days, and 1-3 months. Astrocyte proliferation was detectable at 3-7 days, and vimentin was expressed in astrocytes that surrounded and/or protruded into the damaged sites. The NeuN-positive cells also reappeared in the injury sites where astrocytes reappeared. Taken together, these results suggest that astroycte survival and/or gliosis in the injured brain may be critical for neuronal survival and may prevent delayed neuronal death in the injured brain.

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“…Astrocytes provide neurons with glucose and neurotrophic factors, and protect neurons from oxidative stress and excitotoxicity through glutathione (GSH) production, glutamate and potassium uptake, and modulation of water content [11-17]. Accordingly, it has been reported that ablation of astrocytes augments traumatic neuronal damage, and that transplantation of astrocytes diminishes brain damage [18,19]. …”

Section: Introductionmentioning

confidence: 99%

Spatial and temporal correlation in progressive degeneration of neurons and astrocytes in contusion-induced spinal cord injury

Min

Jeong

Kim

et al. 2012

J Neuroinflammation

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BackgroundTraumatic spinal cord injury (SCI) causes acute neuronal death followed by delayed secondary neuronal damage. However, little is known about how microenvironment regulating cells such as microglia, astrocytes, and blood inflammatory cells behave in early SCI states and how they contribute to delayed neuronal death.MethodsWe analyzed the behavior of neurons and microenvironment regulating cells using a contusion-induced SCI model, examining early (3–6 h) to late times (14 d) after the injury.ResultsAt the penumbra region close to the damaged core (P1) neurons and astrocytes underwent death in a similar spatial and temporal pattern: both neurons and astrocytes died in the medial and ventral regions of the gray matter between 12 to 24 h after SCI. Furthermore, mRNA and protein levels of transporters of glutamate (GLT-1) and potassium (Kir4.1), functional markers of astrocytes, decreased at about the times that delayed neuronal death occurred. However, at P1 region, ramified Iba-1+ resident microglia died earlier (3 to 6 h) than neurons (12 to 24 h), and at the penumbra region farther from the damaged core (P2), neurons were healthy where microglia were morphologically activated. In addition, round Iba-1/CD45-double positive monocyte-like cells appeared after neurons had died, and expressed phagocytic markers, including mannose receptors, but rarely expressed proinflammatory mediators.ConclusionLoss of astrocyte function may be more critical for delayed neuronal death than microglial activation and monocyte infiltration.

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Transplantation of cultured astrocytes attenuates degenerative changes in rats with kainic acid-induced brain damage

Cited by 5 publications

References 13 publications

Astrogliosis Is a Possible Player in Preventing Delayed Neuronal Death

Astrogliosis Is a Possible Player in Preventing Delayed Neuronal Death

Absence of Delayed Neuronal Death in ATP-Injected Brain: Possible Roles of Astrogliosis

Spatial and temporal correlation in progressive degeneration of neurons and astrocytes in contusion-induced spinal cord injury

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