Nicotine and Cotinine Modulate Cerebral Microvascular Permeability and Protein Expression of ZO-1 through Nicotinic Acetylcholine Receptors Expressed on Brain Endothelial Cells

Abbruscato, Thomas J.; Lopez, Steve P.; Mark, Karen S.; Hawkins, Brian T.; Davis, Thomas P.

doi:10.1002/jps.10256

Cited by 157 publications

(148 citation statements)

References 46 publications

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“…82 Loss of ZO-1, or its dissociation from the junctional complex, was shown to be associated with increased barrier permeability. 42,[83][84][85] We noted that during the first week post-injury, probably related to the pronounced BM detachment, ZO-1 distribution in the lesion epicenter appeared more strongly affected after ChABC treatment. Note that at this time post-injury, we also observed a slight decrease not only in laminin, but also in AHNAK protein, which colocalizes with ZO-1 at TJs.…”

Section: Discussionmentioning

confidence: 67%

Astrocytic and Vascular Remodeling in the Injured Adult Rat Spinal Cord after Chondroitinase ABC Treatment

Milbreta

Boxberg

Mailly

et al. 2014

Journal of Neurotrauma

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Upregulation of extracellular chondroitin sulfate proteoglycans (CSPG) is a primary cause for the failure of axons to regenerate after spinal cord injury (SCI), and the beneficial effect of their degradation by chondroitinase ABC (ChABC) is widely documented. Little is known, however, about the effect of ChABC treatment on astrogliosis and revascularization, two important factors influencing axon regrowth. This was investigated in the present study. Immediately after a spinal cord hemisection at thoracic level 8-9, we injected ChABC intrathecally at the sacral level, repeated three times until 10 days post-injury. Our results show an effective cleavage of CSPG glycosaminoglycan chains and stimulation of axonal remodeling within the injury site, accompanied by an extended period of astrocyte remodeling (up to 4 weeks). Interestingly, ChABC treatment favored an orientation of astrocytic processes directed toward the injury, in close association with axons at the lesion entry zone, suggesting a correlation between axon and astrocyte remodeling. Further, during the first weeks post-injury, ChABC treatment affected the morphology of laminin-positive blood vessel basement membranes and vessel-independent laminin deposits: hypertrophied blood vessels with detached or duplicated basement membrane were more numerous than in lesioned untreated animals. In contrast, at later time points, laminin expression increased and became more directly associated with newly formed blood vessels, the size of which tended to be closer to that found in intact tissue. Our data reinforce the idea that ChABC injection in combination with other synergistic treatments is a promising therapeutic strategy for SCI repair.

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Section: Discussionmentioning

confidence: 67%

Astrocytic and Vascular Remodeling in the Injured Adult Rat Spinal Cord after Chondroitinase ABC Treatment

Milbreta

Boxberg

Mailly

et al. 2014

Journal of Neurotrauma

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“…122 Notably, these BBB endothelial responses were blocked by nicotinic receptor antagonists. 116,123 Moreover, a multitude of studies assessing the independent effects of nicotine in experimental stroke models strongly indicate that nicotine plays a significant role in TS-enhanced risk for stroke and worsened neurological outcome in post-ischemic injuries. For instance, chronic nicotine exposure aggravated TJ disruption and ionic imbalance within the BBB microenvironment following ischemic hypoxia 116,124,125 and intensified strokeassociated brain edema and neuronal injury.…”

Section: Smoking and Cerebrovascular Complications: Does Nicotine Havmentioning

confidence: 99%

Drugs of abuse and blood-brain barrier endothelial dysfunction: A focus on the role of oxidative stress

Sajja

Rahman

Cucullo

2015

J Cereb Blood Flow Metab

119

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Psychostimulants and nicotine are the most widely abused drugs with a detrimental impact on public health globally. While the long-term neurobehavioral deficits and synaptic perturbations are well documented with chronic use of methamphetamine, cocaine, and nicotine, emerging human and experimental studies also suggest an increasing incidence of neurovascular complications associated with drug abuse. Short-or long-term administration of psychostimulants or nicotine is known to disrupt blood-brain barrier (BBB) integrity/function, thus leading to an increased risk of brain edema and neuroinflammation. Various pathophysiological mechanisms have been proposed to underlie drug abuse-induced BBB dysfunction suggesting a central and unifying role for oxidative stress in BBB endothelium and perivascular cells. This review discusses drug-specific effects of methamphetamine, cocaine, and tobacco smoking on brain microvascular crisis and provides critical assessment of oxidative stress-dependent molecular pathways focal to the global compromise of BBB. Additionally, given the increased risk of human immunodeficiency virus (HIV) encephalitis in drug abusers, we have summarized the synergistic pathological impact of psychostimulants and HIV infection on BBB integrity with an emphasis on unifying role of endothelial oxidative stress. This mechanistic framework would guide further investigations on specific molecular pathways to accelerate therapeutic approaches for the prevention of neurovascular deficits by drugs of abuse.

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“…The risk of stroke is dose-dependent and increases from 3.57 to 4.65 with 5 to 15 cigarettes per day (Bonita et al, 1999). In addition to enhanced risk factors for brain ischemia, there is a growing body of evidence that nicotine alters BBB permeability characteristics that have a direct influence on stroke outcome and the pathophysiology of brain ischemia (Abbruscato et al, 2002Hawkins et al, 2002Hawkins et al, , 2004. More importantly, stroke outcome has been shown to be worsened by increased edema observed in a 2-week exposure to nicotine after focal ischemia in rats (Wang et al, 1997).…”

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confidence: 99%

Nicotine Exacerbates Brain Edema during In Vitro and In Vivo Focal Ischemic Conditions

Paulson¹,

Yang²,

Selvaraj³

et al. 2009

J Pharmacol Exp Ther

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We have previously shown that nicotine, the addictive component of tobacco products, alters the blood-brain barrier (BBB) Na ϩ ,K ϩ ,2Cl Ϫ cotransporter (NKCC) during in vitro hypoxiaaglycemia exposure. Attenuation of abluminal NKCC suggests that accumulation of ions in the brain extracellular fluid would result in an increase of fluid or cytotoxic edema in the brain during hypoxia-aglycemia or stroke conditions. To further investigate whether nicotine products have the potential to worsen stroke outcome by increasing edema formation, two separate models to mimic stroke conditions were utilized to decipher the effects of short-term and long-term administrations of nicotine products on brain edema following stroke. Oxygen glucose deprivation (OGD) was studied in rat hippocampal slices with short-term or long-term exposure to nicotine and cigarette smoke constituents. During short-term exposure, the presence of nicotine at a concentration mimicking heavy smokers increased water content of hippocampal slices during OGD. Furthermore, long-term 1-week administration of nicotine increased water content in hippocampal slices that could be attenuated with nicotine acetylcholine receptor (nAChR) antagonists, suggesting nicotine increase edema during OGD via nAChRs. A second model of focal ischemia, middle cerebral artery occlusion, showed an increase of infarct size during short-term exposure to nicotine and an increase of edema during both short-term and long-term administration of nicotine, compared with saline controls. These findings support the paradigm that nicotine products not only increase the incidence of stroke but also have the potential to worsen stroke outcome by increased edema formation.

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Nicotine and Cotinine Modulate Cerebral Microvascular Permeability and Protein Expression of ZO-1 through Nicotinic Acetylcholine Receptors Expressed on Brain Endothelial Cells

Cited by 157 publications

References 46 publications

Astrocytic and Vascular Remodeling in the Injured Adult Rat Spinal Cord after Chondroitinase ABC Treatment

Astrocytic and Vascular Remodeling in the Injured Adult Rat Spinal Cord after Chondroitinase ABC Treatment

Drugs of abuse and blood-brain barrier endothelial dysfunction: A focus on the role of oxidative stress

Nicotine Exacerbates Brain Edema during In Vitro and In Vivo Focal Ischemic Conditions

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