Morphine attenuates neuroinflammation and blood-brain barrier disruption following traumatic brain injury through the opioidergic system.

Endogenous opiates are suggested to have a role in the pathophysiology of traumatic brain injury (TBI). Furthermore, administration of opioidergic agents in TBI injured animals have been shown to affect the brain injury and provide neuroprotection post-TBI. This study aims to investigate the potential neuroprotective effects of morphine through inhibition of neuroinflammatory pathways in acute severe TBI. Male Wistar rats were divided into seven groups (24 rats per group): Sham, Vehicle (TBI + intraperitoneal (i.p) injection of normal saline), TBI + i.p injection of morphine in 1, 5 and 10 mg/kg doses (MOR 1, MOR 5 and MOR 10 groups), TBI + morphine (5 mg/kg i.p) + Naloxone (NAL + MOR), and TBI + morphine (5 mg/kg i.p) + Naltrindole (NALT + MOR). A severe diffuse TBI model (weight dropping Marmarou model) was used to induce TBI in rats. The veterinary coma scale (VCS), beam-walk, and beam-balance tasks were used to assess short-term neurological deficits. Histolopathological changes of brain tissue was evaluated using light microscopy and hematoxilin and eosin staining. Blood-Brain barrier (BBB) disruption was evaluated by the Evans Blue method 6 h post-injury. Brain water content and cerebrospinal fluid (CSF) content of IL-1ß and IL-10 were assessed by the wet-dry method and enzyme-linked immunosorbent assay (ELISA), respectively. Morphine (1 and 5 mg/kg doses) attenuated BBB leakage, improved VCS score, pathological changes of brain tissue, and vestibulomotor function compared to the vehicle group (p < 0.0001). Only 5 mg/kg morphine attenuated brain edema (p < 0.0001). Furthermore, 1 and 5 mg/kg morphine significantly changed CSF concentration of IL-1ß and IL-10 compared to the vehicle group (p < 0.0001). Inhibition of opioid receptors by naloxone and naltrindole abolished morphine neuroprotective effects (p < 0.0001 vs. MOR 5 group). This study suggests that morphine administration inhibits TBI-mediated neuroinflammation via opioid receptors and improves neurobehavioral function following TBI, which provides a potential therapeutic opportunity in the treatment of traumatic brain injury.

Calcium and Heart Failure: How Did We Get Here and Where Are We Going?

The occurrence and prevalence of heart failure remain high in the United States as well as globally. One person dies every 30 s from heart disease. Recognizing the importance of heart failure, clinicians and scientists have sought better therapeutic strategies and even cures for end-stage heart failure. This exploration has resulted in many failed clinical trials testing novel classes of pharmaceutical drugs and even gene therapy. As a result, along the way, there have been paradigm shifts toward and away from differing therapeutic approaches. The continued prevalence of death from heart failure, however, clearly demonstrates that the heart is not simply a pump and instead forces us to consider the complexity of simplicity in the pathophysiology of heart failure and reinforces the need to discover new therapeutic approaches.