Haloperidol Brain injury

The administration of haloperidol (HAL) once daily for 19 days after experimental traumatic brain injury (TBI) impedes recovery and attenuates the efficacy of environmental enrichment (EE). However, it is unknown how intermittent administration of HAL affects the recovery process when paired with EE. Addressing the uncertainty is relevant because daily HAL is not always warranted to manage TBI-induced agitation in the clinic, and indeed intermittent therapy may be a more common approach. Hence, the aim of the study was to test the hypothesis that intermittent HAL would neither impair recovery in standard (STD)-housed controls nor attenuate the efficacy of EE...

Many individuals in post-traumatic amnesia (PTA) following traumatic brain injury (TBI) experience neurobehavioral symptoms (NBS) in addition to disorientation and amnesia. These symptoms are associated with low rehabilitation engagement, self-inflicted harm, and risk of violence. The aim of this systematic review was to evaluate the efficacy and harms of pharmacological interventions for NBS in PTA following TBI in adults. Studies in English published before December 2017 were reviewed. Six databases were searched, with additional hand searching of key journals, clinical trials registries, and international drug regulators...

Traumatic brain injury (TBI) is a significant health care issue that affects over ten million people worldwide. Treatment options are limited with numerous failures resulting from single therapies. Fortunately, several preclinical studies have shown that combination treatment strategies may afford greater improvement and perhaps can lead to successful clinical translation, particularly if one of the therapies is neurorehabilitation. The aim of this review is to highlight TBI studies that combined environmental enrichment (EE), a preclinical model of neurorehabilitation, with pharmacotherapies...

OBJECTIVE: This study aimed to compare the presence of agitation in traumatic brain injury patients treated with amantadine with those not treated with amantadine in the intensive care unit (ICU). METHODS: This was a retrospective cohort study conduced in a trauma ICU of a tertiary care institution in the United States. Patients who received amantadine were compared with patients who did not receive amantadine. The primary outcome measure was the presence of agitation, defined as the Richmond Agitation Sedation Scale score of +2 or higher...

Antipsychotic drugs, such as haloperidol (HAL), are prescribed in the clinic to manage traumatic brain injury (TBI)-induced agitation. While preclinical studies have consistently shown that once-daily administration of HAL hinders functional recovery after TBI in male rats, its effects in females are unknown. Hence, the objective of this study was to directly compare neurobehavioral and histological outcomes in both sexes to determine whether the reported deleterious effects of HAL extend to females. Anesthetized adult female and male rats received either a controlled cortical impact (CCI) or sham injury and then were randomly assigned to a dosing regimen of HAL (0...

Glial cells play a critical role in neuronal support which includes the production and release of the neurotrophin brain-derived neurotrophic factor (BDNF). Activation of the sigma-1 receptor (S1R) has been shown to attenuate inflammatory stress-mediated brain injuries, and there is emerging evidence that this may involve a BDNF-dependent mechanism. In this report we studied S1R-mediated BDNF release from human astrocytic glial cells. Astrocytes express the S1R, which mediates BDNF release when stimulated with the prototypical S1R agonists 4-PPBP and (+)-SKF10047...

Neuropathic pain is caused by a primary lesion, dysfunction, or transitory perturbation in the peripheral or central nervous system. In this study, we investigated the hesperidin antihyperalgesic effects alone or combined with diosmin in a model of neuropathic pain to corroborate a possible synergistic antinociceptive activity. Mechanical and thermal hyperalgesia were assessed in the aesthesiometer and plantar tests, respectively, after chronic constriction injury (CCI) model in rats receiving hesperidin (HS, 5 doses from 10 to 1000 mg/kg) alone or combined with diosmin (DS, 10 and 100 mg/kg) in comparison to gabapentin (31...

Traumatic brain injury (TBI)-induced agitation and aggression pose major obstacles to clinicians in the acute hospital and rehabilitation settings. Thus, management of these symptoms is crucial. Antipsychotic drugs (APDs) are a common treatment approach for alleviating these symptoms. However, previous preclinical TBI studies have indicated that daily and chronic administration of these drugs (e.g., haloperidol; HAL) can exacerbate cognitive and motor deficits. Quetiapine (QUE) is an atypical APD that differs from many typical APDs, such as HAL, in its relatively rapid dissociation from the D2 receptor...

Haloperidol is an effective antipsychotic agent, but it causes Parkinsonian-like extrapyramidal symptoms in the majority of treated subjects. To address this treatment-limiting toxicity, we analyzed a murine genetic model of haloperidol-induced toxicity (HIT). Analysis of a panel of consomic strains indicated that a genetic factor on chromosome 10 had a significant effect on susceptibility to HIT. We analyzed a whole-genome SNP database to identify allelic variants that were uniquely present on chromosome 10 in the strain that was previously shown to exhibit the highest level of susceptibility to HIT...

Environmental enrichment (EE) confers significant benefits after experimental traumatic brain injury (TBI). In contrast, the antipsychotic drug (APD) haloperidol (HAL) exerts deleterious effects on neurobehavioral and cognitive recovery. Neurorehabilitation and management of agitation, however, are integral components of the treatment strategy for patients with TBI. Hence, the goal of this study was to determine how the two therapeutic approaches interact and influence motor and cognitive recovery. Anesthetized adult male rats received a controlled cortical impact (2...

Glutamate-induced excitotoxicity via the N-methyl-d-aspartate (NMDA) receptor is an important factor in the pathogenesis of perinatal brain injury. The sigma-1 receptor on the endoplasmic reticulum (ER) has been known to affect the function of the NMDA receptor. 4-Phenyl-1-(4-phenylbutyl)piperidine (PPBP) has been investigated as a sigma-1 receptor agonist for several decades. An article using PPBP in a model of preterm brain injury was published in Experimental Neurology. The authors reported that PPBP protected against glutamate-induced excitotoxicity in primary hippocampal neurons...

Antipsychotic drugs (APDs) are provided in the clinic to manage traumatic brain injury (TBI)-induced agitation and aggression. Experimental TBI studies consistently show that daily administration of the APDs, haloperidol (HAL) and risperidone (RISP), hinder recovery. However, it is unknown how long the adverse effects remain after cessation of treatment. To elucidate this clinically relevant issue, anesthetized male rats were randomly assigned to four TBI (controlled cortical impact) and four sham groups administered HAL (0...

Driving under methylenedioxymethamphetamine (MDMA) influence increases the risk of being involved in a car accident, which in turn can lead to traumatic brain injury. The behavioral deficits after traumatic brain injury (TBI) are closely connected to dopamine pathway dysregulation. We have previously demonstrated in mice that low MDMA doses prior to mTBI can lead to better performances in cognitive tests. The purpose of this study was to assess in mice the changes in the dopamine system that occurs after both MDMA and minimal traumatic brain injury (mTBI)...

Premature birth represents a clinical situation of risk for brain injury. The diversity of pathophysiological processes complicates efforts to find effective therapeutic strategies. Excitotoxicity is one important factor in the pathogenesis of preterm brain injury. The observation that sigma-1 receptor agonists possess neuroprotective potential, at least partly mediated by a variety of anti-excitotoxic mechanisms, has generated great interest in targeting those receptors to counteract brain injury. The objective of this study was to evaluate the effect of the highly specific sigma-1 receptor agonist, 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) to protect against excitotoxic developmental brain injury in vivo and in vitro...

Delirium is 1.5 to 4.1 times as likely in intensive care unit patients when they are mechanically ventilated. While progress in treatment has occurred, delirium is still a major problem in mechanically ventilated patients. Based on studies of a murine mechanical ventilation model, we summarize evidence here for a novel mechanism by which such ventilation can quickly initiate brain damage likely to cause cognitive deficits expressed as delirium. That mechanism consists of aberrant vagal sensory input driving sustained dopamine D2 receptor (D2R) signaling in the hippocampal formation, which induces apoptosis in that brain area within 90 min without causing hypoxia, oxidative stress, or inflammatory responses...

Delirium is a neuropsychiatric condition that may complicate any visceral disease. Its rate is especially high among patients with inflammatory diseases or metabolic disturbances and in the elderly. Brain injury concurrent with an abnormal stress response underlies the development of delirium. The clinical picture of delirium is characterized by clouding of consciousness accompanied by global cognitive and behavioral changes. According to the nature of changes in motor behavior, delirium is divided into hyperactive, hypoactive, and mixed subtypes...

RATIONALE: Critically ill patients frequently develop neuropsychological disturbances including acute delirium or memory impairment. The need for mechanical ventilation is a risk factor for these adverse events, but a mechanism that links lung stretch and brain injury has not been identified. OBJECTIVES: To identify the mechanisms that lead to brain dysfunction during mechanical ventilation. METHODS: Brains from mechanically ventilated mice were harvested, and signals of apoptosis and alterations in the Akt survival pathway were studied...

Schizophrenia is recognized as a psychiatric disorder that causes the most pronounced disturbances of cognition and social integration. In the etiopathogenesis of the disease, genetic, neurobiological and vascular factors are involved. Functional integrity of the brain can be correlated with the integrity of the blood-brain barrier (BBB), and the dysfunction of this barrier is an indicator that suggests neurodevelopmental abnormalities, injuries of various etiologies and dysfunctions within the small vessels of the brain that disrupt the calcium homeostasis...

We hypothesize the interaction between antipsychotic medications and regulation of extracellular glutamate which has gone largely unnoticed in the medical community has significant clinical importance. Typical antipsychotic medications such as haloperidol elevate extracellular glutamate because they exert antagonist effects on dopamine D(2) and serotonin 5HT(1A) receptors. In contrast, serotonin 5HT(2A) receptor antagonists inhibit glutamate release. Glutamate is potentially excitotoxic through effects on ionotropic receptor channels and may exert synergistic effects with other neurotoxic pathways...

Introduction. Stroke is a leading cause of mortality and morbidity in the United States. About 20% of the stroke is hemorrhagic and about 50% of these is due to aneurysmal subarachnoid hemorrhage. A troublesome neuropsychiatric complication of subarachnoid hemorrhage is agitation/aggression. Case Presentation. A 45-year-old man with no prior psychiatric history, sustained subarachnoid hemorrhage. After initial stabilization for 2 days, he underwent craniotomy and clipping of anterior cerebral communicating artery aneurysm...