Ultrastructure of blood–brain barrier and blood–spinal cord barrier in SOD1 mice modeling ALS

Garbuzova‐Davis, Svitlana; Haller, Edward; Saporta, Samuel; Kolomey, Irina; Nicosia, Santo V.; Sanberg, Paul R.

doi:10.1016/j.brainres.2007.04.044

Cited by 206 publications

(191 citation statements)

References 39 publications

Supporting

Mentioning

182

Contrasting

Unclassified

Order By: Relevance

“…In this same study, IL-1β was also increased in microglia and this increase was implicated in increased astrogliosis (Griffin et al, 1989). Moreover, astrocytes have also been targeted as potential contributors to motor neuron death in animal models of amyotrophic lateral sclerosis (ALS) through secretion of astrocytespecific factor(s) (Nagai et al, 2007) and through a breakdown in the blood-brain barrier due to swelling of astrocyte end foot processes (Garbuzova-Davis et al, 2007). Further, reactive astrocytes have been implicated in the neuropathophysiology observed in Parkinson's disease (for review see Mrak and Griffin, 2005).…”

Section: Discussionmentioning

confidence: 79%

Effects of estrogen receptor agonists on regulation of the inflammatory response in astrocytes from young adult and middle-aged female rats

Lewis¹,

Johnson²,

Stohlgren³

et al. 2008

Journal of Neuroimmunology

View full text Add to dashboard Cite

Estrogen has been shown to attenuate the inflammatory response following injury or lipopolysaccharide treatment in several organ systems. Estrogen's actions are transduced through two estrogen receptor sub-types, estrogen receptor (ER) -alpha and estrogen receptor-beta, whose actions may be overlapping or independent of each other. The present study examined the effects of ERα-and ERβ-specific ligands in regulating the inflammatory response in primary astrocyte cultures. Pre-treatment with 17β-estradiol (ERα/ERβ agonist), HPTE (ERα agonist/ERβ antagonist) and DPN (ERβ agonist) led to attenuation of IL-1β, TNFα, and MMP-9 in astrocyte media derived from young adult (3-4 mos.) and reproductive senescent female (9-11 mos., acyclic) astrocyte cultures, while pretreatment with PPT (ERα agonist) attenuated IL-1β (but not TNFα or MMP-9) in both young and senescent-derived astrocyte cultures. Our previous work determined that 17β-estradiol was unable to attenuate the LPS-induced increase in IL-1β in olfactory bulb primary microglial cultures derived from either young adult or reproductive senescent females. In young adult-derived microglial cultures, the LPS-induced increase in IL-1β was not attenuated by pre-treatment with 17β-estradiol, PPT or HPTE. Interestingly, the ERβ agonist, DPN significantly decreased IL-1β following LPS treatment in young adult-derived microglia. Thus while both microglia and astrocytes synthesize and release inflammatory mediators, the present data shows that compounds which bind ERβ are more effective in attenuating proinflammatory cytokines in both cell types and may therefore be a more effective agent for future therapeutic use.

show abstract

Section: Discussionmentioning

confidence: 79%

Effects of estrogen receptor agonists on regulation of the inflammatory response in astrocytes from young adult and middle-aged female rats

Lewis¹,

Johnson²,

Stohlgren³

et al. 2008

Journal of Neuroimmunology

View full text Add to dashboard Cite

show abstract

“…Transgenic mice that have a glycine 93 to alanine 93 (G93A) mutation develop an amyotrophic lateral sclerosis-like syndrome. Disruption of BBB and blood-spinal cord barrier was seen in areas of motor neuron degeneration in G93A mice at both early and late stages of disease, and capillary ultrastructure revealed that endothelial cell membrane and/or basement membrane damage occurred, and was followed by vascular leakage (Garbuzova-Davis et al, 2007). Superoxide dismutase 1 mutant mice with disrupted bloodspinal cord barrier had reduced levels of the tight junction proteins zonula occludens 1, occludin and claudin-5 between endothelial cells, which caused microhemorrhages and release of neurotoxic hemoglobin-derived products.…”

Section: Blood-brain Barrier Disruption In Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Neurological Diseases in Relation to the Blood–Brain Barrier

Rosenberg

2012

J Cereb Blood Flow Metab

375

270

View full text Add to dashboard Cite

Disruption of the blood-brain barrier (BBB) has an important part in cellular damage in neurological diseases, including acute and chronic cerebral ischemia, brain trauma, multiple sclerosis, brain tumors, and brain infections. The neurovascular unit (NVU) forms the interface between the blood and brain tissues. During an injury, the cascade of molecular events ends in the final common pathway for BBB disruption by free radicals and proteases, which attack membranes and degrade the tight junction proteins in endothelial cells. Free radicals of oxygen and nitrogen and the proteases, matrix metalloproteinases and cyclooxgyenases, are important in the early and delayed BBB disruption as the neuroinflammatory response progresses. Opening of the BBB occurs in neurodegenerative diseases and contributes to the cognitive changes. In addition to the importance of the NVU in acute injury, angiogenesis contributes to the recovery process. The challenges to treatment of the brain diseases involve not only facilitating drug entry into the brain, but also understanding the timing of the molecular cascades to block the early NVU injury without interfering with recovery. This review will describe the molecular and cellular events associated with NVU disruption and potential strategies directed toward restoring its integrity.

show abstract

“…More specifically, Zhong et al showed increased endothelial permeability associated with impaired expression of tight junction proteins. In parallel, Garbuzova-Davis et al, also working on SOD1 mice model, through a thorough blood-spinal cord-barrier ultrastructure analysis showed that not only endothelial cells were degenerated and swollen but also that basement membrane and astrocyte end-foot processes around microvasculature were affected (Garbuzova-Davis et al, 2007b). In addition, a recent work studying Kir4.1 channel in the spinal cord of SOD1 mutated transgenic mice noticed an increase in AQP4 protein (Kaiser et al, 2006).…”

mentioning

confidence: 95%

Aquaporin‐4 Overexpression in Rat ALS Model

Nicaise

Soyfoo

Authelet

et al. 2008

The Anatomical Record

View full text Add to dashboard Cite

Onset of motoneuron death characterizing amyotrophic lateral sclerosis (ALS) is closely linked to modified astrocytic and glial environments. Here, we show that in the spinal cord from transgenic rat overexpressing mutated human SOD1, aquaporin-4 mRNA and protein are specifically overexpressed in the gray matter at end stage of disease. Immunohistochemistry and double immunofluorescence allowed to detect, in the spinal cord gray matter of the ALS rat, increased aquaporin-4 surrounding both vessel and motoneuron perikarya. The use of pre-embedding immunohistochemistry at electron microscopic level confirmed such localization associated with swollen astrocytic processes surrounding the vessels. The AQP4 immunohistochemical labeling surrounding several motoneuron perikarya was only seen in ALS rats. Identification of this AQP4-positive cellular type remains unclear.

show abstract

Ultrastructure of blood–brain barrier and blood–spinal cord barrier in SOD1 mice modeling ALS

Cited by 206 publications

References 39 publications

Effects of estrogen receptor agonists on regulation of the inflammatory response in astrocytes from young adult and middle-aged female rats

Effects of estrogen receptor agonists on regulation of the inflammatory response in astrocytes from young adult and middle-aged female rats

Neurological Diseases in Relation to the Blood–Brain Barrier

Aquaporin‐4 Overexpression in Rat ALS Model

Contact Info

Product

Resources

About