Cocaine-Induced Breakdown of the Blood–Brain Barrier and Neurotoxicity

Sharma, Hari Shanker; Mureșanu, Dafin F.; Sharma, Aruna; Patnaik, Ranjana

doi:10.1016/s0074-7742(09)88011-2

Cited by 93 publications

(55 citation statements)

References 123 publications

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“…It is believed that psychostimulant induced abnormal expression of HSP could reflect the state of specific cellular stress in the CNS. However, the functional significance of such findings is still not well known [9, 11-13, 45]. …”

Section: Discussionmentioning

confidence: 99%

“…However, observed a profound increase in heat shock protein 72 kD (HSP) expression in the areas showing neuronal distortion and damage [9, 11, 12]. This indicates that cellular stress caused by morphine withdrawal may play important determining role in the BBB dysfunction [13-18] and subsequently neuronal and glial damage in the brain [19-24]. It is therefore possible that drugs or therapeutic agents that are able to reduce the stress response caused by morphine dependence or withdrawal could be able to attenuate these neurodegenerative changes.…”

Section: Introductionmentioning

confidence: 99%

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Cerebrolysin Attenuates Heat Shock Protein (HSP 72 KD) Expression in the Rat Spinal Cord Following Morphine Dependence and Withdrawal: Possible New Therapy for Pain Management

Sharma¹,

Ali²,

Patnaik³

et al. 2011

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The possibility that pain perception and processing in the CNS results in cellular stress and may influence heat shock protein (HSP) expression was examined in a rat model of morphine dependence and withdrawal. Since activation of pain pathways result in exhaustion of growth factors, we examined the influence of cerebrolysin, a mixture of potent growth factors (BDNF, GDNF, NGF, CNTF etc,) on morphine induced HSP expression. Rats were administered morphine (10 mg/kg, s.c. /day) for 12 days and the spontaneous withdrawal symptoms were developed by cessation of the drug administration on day 13th that were prominent on day 14th and continued up to day 15th (24 to 72 h periods). In a separate group of rats, cerebrolysin was infused intravenously (5 ml/kg) once daily from day one until day 15th. In these animals, morphine dependence and withdrawal along with HSP immunoreactivity was examined using standard protocol. In untreated group mild HSP immunoreaction was observed during morphine tolerance, whereas massive upregulation of HSP was seen in CNS during withdrawal phase that correlated well with the withdrawal symptoms and neuronal damage. Pretreatment with cerebrolysin did not affect morphine tolerance but reduced the HSP expression during this phase. Furthermore, cerebrolysin reduced the withdrawal symptoms on day 14th to 15th. Taken together these observations suggest that cellular stress plays an important role in morphine induced pain pathology and exogenous supplement of growth factors, i.e. cerebrolysin attenuates HSP expression in the CNS and induce neuroprotection. This indicates a new therapeutic role of cerebrolysin in the pathophysiology of drugs of abuse, not reported earlier.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cerebrolysin Attenuates Heat Shock Protein (HSP 72 KD) Expression in the Rat Spinal Cord Following Morphine Dependence and Withdrawal: Possible New Therapy for Pain Management

Sharma¹,

Ali²,

Patnaik³

et al. 2011

Self Cite

View full text Add to dashboard Cite

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“…At high doses, cocaine is markedly more dangerous than other central nervous system stimulants, including amphetamines [15], and can cause sudden cardiac death through its effect on sodium channels and local anesthetic actions [13,14,16]. Cocaine crosses the blood–brain-barrier perhaps better than other psychoactive chemicals and may even induce its breakdown [17,18]. In addition, cocaine blocks reuptake of catecholamines in the presynaptic neurons in the central and peripheral nervous systems, resulting in increased catecholamines, sympathetic output and stimulation [2,19].…”

Section: Pharmacodynamics Of Cocainementioning

confidence: 99%

Vascular disease in cocaine addiction

et al. 2017

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Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by vascular pathology. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use disorder of that period, now aging. Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best. We review major postmortem and in vitro studies documenting cocaine-induced vascular toxicity. PubMed and Academic Search Complete were used with relevant terms. Findings consist of the major mechanisms of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine. The etiology underlying cocaine's acute and chronic vascular effects is multifactorial, spanning hypertension, impaired homeostasis and platelet function, thrombosis, thromboembolism, and alterations in blood flow. Early detection of vascular disease in cocaine addiction by multimodality imaging is discussed. Treatment may be similar to indications in patients with traditional risk-factors, with few exceptions such as enhanced supportive care and use of benzodiazepines and phentolamine for sedation, and avoiding β-blockers. Given the vascular toxicity cocaine induces, further compounded by smoking and alcohol comorbidity, and interacting with aging of the crack generation, there is a public health imperative to identify pre-symptomatic markers of vascular impairments in cocaine addiction and employ preventive treatment to reduce silent disease progression.

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“…85,86 It is widely demonstrated that elevated levels of oxidative/inflammatory stress pathways and endothelial activation are the primary pathological processes implicated in cocainemediated BBB disruption. 85,89 Indeed, cocaine exhibits cell-specific and concentration sensitive multimodal interactions with endothelial, immune, and neuroendocrine cells that strongly converge on BBB dysfunction and increased brain extravasation of reactive molecules and immune cells. 91,92 It should also be noted that intense hyperthermia associated with cocaine administration can also evoke potential BBB damage and brain edema.…”

Section: Cocaine Abuse and Blood-brain Barrier Impairmentmentioning

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

117

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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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Cocaine-Induced Breakdown of the Blood–Brain Barrier and Neurotoxicity

Cited by 93 publications

References 123 publications

Cerebrolysin Attenuates Heat Shock Protein (HSP 72 KD) Expression in the Rat Spinal Cord Following Morphine Dependence and Withdrawal: Possible New Therapy for Pain Management

Cerebrolysin Attenuates Heat Shock Protein (HSP 72 KD) Expression in the Rat Spinal Cord Following Morphine Dependence and Withdrawal: Possible New Therapy for Pain Management

Vascular disease in cocaine addiction

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

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