Astrogliosis (also known as astrocytosis or referred to as reactive astrogliosis) is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons from central nervous system (CNS) trauma, infection, ischemia, stroke, autoimmune responses or neurodegenerative disease. In healthy neural tissue, astrocytes play critical roles in energy provision, regulation of blood flow, homeostasis of extracellular fluid, homeostasis of ions and transmitters, regulation of synapse function and synaptic remodeling.
Causes
Reactive astrogliosis is a spectrum of changes in astrocytes that occur in response to all forms of CNS injury and disease. Changes due to reactive astrogliosis vary with the severity of the CNS insult along a graduated continuum of progressive alterations in molecular expression, progressive cellular hypertrophy, proliferation and scar formation.
Functions and effects
Reactive astrocytes may benefit or harm surrounding neural and non-neural cells. They undergo a series of changes that may alter astrocyte activities through gain or loss of functions lending to neural protection and repair, glial scarring, and regulation of CNS inflammation. such as uptake of potentially excitotoxic glutamate, adenosine release, and degradation of amyloid β peptides.
Regulation of inflammation
Reactive astrocytes are related to the normal function of astrocytes. Astrocytes are involved in the complex regulation of CNS inflammation that is likely to be context-dependent and regulated by multimodal extra- and intracellular signaling events. They have the capacity to make different types of molecules with either pro- or anti-inflammatory potential in response to different types of stimulation. Astrocytes interact extensively with microglia and play a key role in CNS inflammation. Reactive astrocytes can then lead to abnormal function of astrocytes and affect their regulation and response to inflammation.
Pertaining to anti-inflammatory effects, reactive scar-forming astrocytes help reduce the spread of inflammatory cells during locally initiated inflammatory responses to traumatic injury or during peripherally-initiated adaptive immune responses. Reactive astrocytes respond according to different signals and impact neuronal function. Molecular mediators are released by neurons, microglia, oligodendrocyte lineage cells, endothelia, leukocytes, and other astrocytes in the CNS tissue in response to insults ranging from subtle cellular perturbations to intense tissue injury.
Transporters and channels
The presence of astrocyte glutamate transporters is associated with a reduced number of seizures and diminished neurodegeneration whereas the astrocyte gap junction protein Cx43 contributes to the neuroprotective effect of preconditioning to hypoxia. In addition, AQP4, an astrocyte water channel, plays a crucial role in cytotoxic edema and aggravate outcome after stroke.
- Exacerbation of inflammation via cytokine production
- Production and release of neurotoxic levels of reactive oxygen species
- Release of potentially excitotoxic glutamate
- The potential contribution to seizure genesis
- Compromise of blood–brain barrier function as a result of vascular endothelial growth factor production
- Cytotoxic edema during trauma and stroke through AQP4 overactivity
- Potential for chronic cytokine activation of astrocytes to contribute to chronic pain
Reactive astrocytes have the potential to promote neural toxicity via the generation cytotoxic molecules such as nitric oxide radicals and other reactive oxygen species, Current studies are researching the possible benefits of inhibiting the inflammation caused by reactive gliosis in order to reduce its neurotoxic effects.
Neurotrophins are currently being researched as possible drugs for neuronal protection, as they have been shown to restore neuronal function. For example, a few studies have used nerve growth factors to regain some cholinergic function in patients with Alzheimer's. BB14 was shown to reduce reactive astrogliosis following peripheral nerve injuries in rats by acting on DRG and PC12 cell differentiation.