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Astrocytic modulation of blood brain barrier: perspectives on Parkinson's disease.

Cabezas R, Avila M, Gonzalez J, El-Bachá RS, Báez E, García-Segura LM, Jurado Coronel JC, Capani F, Cardona-Gomez GP, Barreto GE - Front Cell Neurosci (2014)

Bottom Line: Astrocytes are essential for the formation and maintenance of the BBB by providing secreted factors that lead to the adequate association between the cells of the BBB and the formation of strong tight junctions.In this aspect, it has been established that the process of reactive gliosis is a common feature of astrocytes during BBB disruption, which has a detrimental effect on the barrier function and a subsequent damage in neuronal survival.Additionally, we highlight the current and future strategies in astrocyte protection aimed at the development of restorative therapies for the BBB in pathological conditions.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana Bogotá, D.C., Colombia.

ABSTRACT
The blood-brain barrier (BBB) is a tightly regulated interface in the Central Nervous System (CNS) that regulates the exchange of molecules in and out from the brain thus maintaining the CNS homeostasis. It is mainly composed of endothelial cells (ECs), pericytes and astrocytes that create a neurovascular unit (NVU) with the adjacent neurons. Astrocytes are essential for the formation and maintenance of the BBB by providing secreted factors that lead to the adequate association between the cells of the BBB and the formation of strong tight junctions. Under neurological disorders, such as chronic cerebral ischemia, brain trauma, Epilepsy, Alzheimer and Parkinson's Diseases, a disruption of the BBB takes place, involving a lost in the permeability of the barrier and phenotypical changes in both the ECs and astrocytes. In this aspect, it has been established that the process of reactive gliosis is a common feature of astrocytes during BBB disruption, which has a detrimental effect on the barrier function and a subsequent damage in neuronal survival. In this review we discuss the implications of astrocyte functions in the protection of the BBB, and in the development of Parkinson's disease (PD) and related disorders. Additionally, we highlight the current and future strategies in astrocyte protection aimed at the development of restorative therapies for the BBB in pathological conditions.

No MeSH data available.


Related in: MedlinePlus

Protective strategies of astrocytes during BBB disruption. In advanced stages of PD, BBB disruption takes place and causes a lost in barrier permeability, entrance of toxic substances and in some instances immune cell infiltration. Processes such as increased ROS production, reactive gliosis and cellular death will inevitably occur. Astrocytic response to BBB disruption includes the production of antioxidative molecules like GSH and ascorbate, generation of growth factors like Brain derived neurotrophic factor (BDNF) and GDNF that could alleviate the cellular death and promote angiogenesis. Furthermore, astrocytes are important in the genetic regulation of endothelial proteins from the tight junction like Occludin and ZO-1. During chronic brain damage, astrocytes also induce the liberation of cytokines like TNF-α, IL-1B, IL-6, important in microglial activation and neuronal death.
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Figure 2: Protective strategies of astrocytes during BBB disruption. In advanced stages of PD, BBB disruption takes place and causes a lost in barrier permeability, entrance of toxic substances and in some instances immune cell infiltration. Processes such as increased ROS production, reactive gliosis and cellular death will inevitably occur. Astrocytic response to BBB disruption includes the production of antioxidative molecules like GSH and ascorbate, generation of growth factors like Brain derived neurotrophic factor (BDNF) and GDNF that could alleviate the cellular death and promote angiogenesis. Furthermore, astrocytes are important in the genetic regulation of endothelial proteins from the tight junction like Occludin and ZO-1. During chronic brain damage, astrocytes also induce the liberation of cytokines like TNF-α, IL-1B, IL-6, important in microglial activation and neuronal death.

Mentions: Experimental evidence using cellular and animal models have shown that environmental and biological toxins, like α-synuclein, LPS (lipopolysaccharides), herbicides and pesticides like rotenone or MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), can induce both astrogliosis and microgliosis, which is accompanied by altered striatal neuronal morphology, neuronal death, mitochondrial dysfunction and nuclear fragmentation (Langston et al., 1999; Samantaray et al., 2007; Niranjan et al., 2010). Additionally, injection of LPS in rat brains was followed by an increase in the inducible nitric oxide synthase (iNOS), suggesting that chronic glial activation can cause oxidative stress in the brain, similarly to that in neurodegenerative processes like AD and Parkinson (Sugaya et al., 1998; Hirsch et al., 2003; de Oliveira et al., 2011). Similarly, there is clinical evidence showing that astrogliosis is present in different areas of the brain in PD patients, including the SN, the putamen and the hippocampus (Baxendale et al., 1998; Dickson et al., 2002; Dickson, 2012). Finally, some studies have shown that activated glial cells can participate in the death of dopaminergic neurons, probably via activation of apoptosis by cytokines like TNF-α, IL-1B, IL-6 (Figure 2) and interferon-γ and the subsequent production of nitric oxide by the iNOS that may diffuse toward the neurons and induce lipid peroxidation, DNA strands breaks and inhibition of mitochondrial metabolism (Hirsch et al., 2003; Rappold and Tieu, 2010). Released cytokines may bind to TNFR1 and 2, specific receptors in dopaminergic neurons, and activate proapoptotic mechanisms through the activation of caspase 3, caspase 8, and cytochrome C (Hirsch et al., 2003). These results suggest that both the glial reaction and the consequent inflammatory processes could be considered as a promising therapy to reduce neuronal damage during PD (Hirsch et al., 2003).


Astrocytic modulation of blood brain barrier: perspectives on Parkinson's disease.

Cabezas R, Avila M, Gonzalez J, El-Bachá RS, Báez E, García-Segura LM, Jurado Coronel JC, Capani F, Cardona-Gomez GP, Barreto GE - Front Cell Neurosci (2014)

Protective strategies of astrocytes during BBB disruption. In advanced stages of PD, BBB disruption takes place and causes a lost in barrier permeability, entrance of toxic substances and in some instances immune cell infiltration. Processes such as increased ROS production, reactive gliosis and cellular death will inevitably occur. Astrocytic response to BBB disruption includes the production of antioxidative molecules like GSH and ascorbate, generation of growth factors like Brain derived neurotrophic factor (BDNF) and GDNF that could alleviate the cellular death and promote angiogenesis. Furthermore, astrocytes are important in the genetic regulation of endothelial proteins from the tight junction like Occludin and ZO-1. During chronic brain damage, astrocytes also induce the liberation of cytokines like TNF-α, IL-1B, IL-6, important in microglial activation and neuronal death.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4120694&req=5

Figure 2: Protective strategies of astrocytes during BBB disruption. In advanced stages of PD, BBB disruption takes place and causes a lost in barrier permeability, entrance of toxic substances and in some instances immune cell infiltration. Processes such as increased ROS production, reactive gliosis and cellular death will inevitably occur. Astrocytic response to BBB disruption includes the production of antioxidative molecules like GSH and ascorbate, generation of growth factors like Brain derived neurotrophic factor (BDNF) and GDNF that could alleviate the cellular death and promote angiogenesis. Furthermore, astrocytes are important in the genetic regulation of endothelial proteins from the tight junction like Occludin and ZO-1. During chronic brain damage, astrocytes also induce the liberation of cytokines like TNF-α, IL-1B, IL-6, important in microglial activation and neuronal death.
Mentions: Experimental evidence using cellular and animal models have shown that environmental and biological toxins, like α-synuclein, LPS (lipopolysaccharides), herbicides and pesticides like rotenone or MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), can induce both astrogliosis and microgliosis, which is accompanied by altered striatal neuronal morphology, neuronal death, mitochondrial dysfunction and nuclear fragmentation (Langston et al., 1999; Samantaray et al., 2007; Niranjan et al., 2010). Additionally, injection of LPS in rat brains was followed by an increase in the inducible nitric oxide synthase (iNOS), suggesting that chronic glial activation can cause oxidative stress in the brain, similarly to that in neurodegenerative processes like AD and Parkinson (Sugaya et al., 1998; Hirsch et al., 2003; de Oliveira et al., 2011). Similarly, there is clinical evidence showing that astrogliosis is present in different areas of the brain in PD patients, including the SN, the putamen and the hippocampus (Baxendale et al., 1998; Dickson et al., 2002; Dickson, 2012). Finally, some studies have shown that activated glial cells can participate in the death of dopaminergic neurons, probably via activation of apoptosis by cytokines like TNF-α, IL-1B, IL-6 (Figure 2) and interferon-γ and the subsequent production of nitric oxide by the iNOS that may diffuse toward the neurons and induce lipid peroxidation, DNA strands breaks and inhibition of mitochondrial metabolism (Hirsch et al., 2003; Rappold and Tieu, 2010). Released cytokines may bind to TNFR1 and 2, specific receptors in dopaminergic neurons, and activate proapoptotic mechanisms through the activation of caspase 3, caspase 8, and cytochrome C (Hirsch et al., 2003). These results suggest that both the glial reaction and the consequent inflammatory processes could be considered as a promising therapy to reduce neuronal damage during PD (Hirsch et al., 2003).

Bottom Line: Astrocytes are essential for the formation and maintenance of the BBB by providing secreted factors that lead to the adequate association between the cells of the BBB and the formation of strong tight junctions.In this aspect, it has been established that the process of reactive gliosis is a common feature of astrocytes during BBB disruption, which has a detrimental effect on the barrier function and a subsequent damage in neuronal survival.Additionally, we highlight the current and future strategies in astrocyte protection aimed at the development of restorative therapies for the BBB in pathological conditions.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana Bogotá, D.C., Colombia.

ABSTRACT
The blood-brain barrier (BBB) is a tightly regulated interface in the Central Nervous System (CNS) that regulates the exchange of molecules in and out from the brain thus maintaining the CNS homeostasis. It is mainly composed of endothelial cells (ECs), pericytes and astrocytes that create a neurovascular unit (NVU) with the adjacent neurons. Astrocytes are essential for the formation and maintenance of the BBB by providing secreted factors that lead to the adequate association between the cells of the BBB and the formation of strong tight junctions. Under neurological disorders, such as chronic cerebral ischemia, brain trauma, Epilepsy, Alzheimer and Parkinson's Diseases, a disruption of the BBB takes place, involving a lost in the permeability of the barrier and phenotypical changes in both the ECs and astrocytes. In this aspect, it has been established that the process of reactive gliosis is a common feature of astrocytes during BBB disruption, which has a detrimental effect on the barrier function and a subsequent damage in neuronal survival. In this review we discuss the implications of astrocyte functions in the protection of the BBB, and in the development of Parkinson's disease (PD) and related disorders. Additionally, we highlight the current and future strategies in astrocyte protection aimed at the development of restorative therapies for the BBB in pathological conditions.

No MeSH data available.


Related in: MedlinePlus