The Renin Angiotensin System as a Therapeutic Target in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major public health problem, with limited pharmacological options available beyond symptomatic relief. The renin angiotensin system (RAS) is primarily known as a systemic endocrine regulatory system, with major roles controlling blood pressure and fluid homeostasis. Drugs that target the RAS are used to treat hypertension, heart failure and kidney disorders. They have now been used chronically by millions of people and have a favorable safety profile. In addition to the systemic RAS, it is now appreciated that many different organ systems, including the brain, have their own local RAS. The major ligand of the classic RAS, Angiotensin II (Ang II) acts predominantly through the Ang II Type 1 receptor (AT1R), leading to vasoconstriction, inflammation, and heightened oxidative stress. These processes can exacerbate brain injuries. Ang II receptor blockers (ARBs) are AT1R antagonists. They have been shown in several preclinical studies to enhance recovery from TBI in rodents through improvements in molecular, cellular and behavioral correlates of injury. ARBs are now under consideration for clinical trials in TBI. Several different RAS peptides that signal through receptors distinct from the AT1R, are also potential therapeutic targets for TBI. The counter regulatory RAS pathway has actions that oppose those stimulated by AT1R signaling. This alternative pathway has many beneficial effects on cells in the central nervous system, bringing about vasodilation, and having anti-inflammatory and anti-oxidative stress actions. Stimulation of this pathway also has potential therapeutic value for the treatment of TBI. This comprehensive review will provide an overview of the various components of the RAS, with a focus on their direct relevance to TBI pathology. It will explore different therapeutic agents that modulate this system and assess their potential efficacy in treating TBI patients.

Ureteral metastasis from locally invasive, castrate-resistant prostate cancer: A Case report.

Within the text we describe a 66-year-old male with a history of prostate cancer (PCa), incidentally found to have left-sided hydronephrosis and a left ureteral lesion. Ureteroscopy was employed to visualize the lesion, a biopsy was taken, and a double J stent was placed. The lesion was of prostatic origin and the patient was subsequently started on androgen deprivation therapy (ADT). 6 months following the procedure, the patient's PSA had decreased and his hydronephrosis had resolved. We are the first to report treating a ureteral metastasis from PCa and its associated hydronephrosis solely with ADT and double J stenting, respectively.

Medical Student Involvement in Disasters: How Can We Effectively Serve?

During disasters, the roles of physicians, nurses, and ancillary medical staff are defined by their individual certifications, whereas the roles of medical students remain less clear. Medical students are unlicensed physicians-in-training, with variable degrees of skill and knowledge, and thus, their involvement in disaster response has historically varied. In light of the coronavirus disease 2019 pandemic, many junior students were asked to remove themselves from the hospital setting, whereas some senior students graduated early to join the physician workforce. In this article, the authors will examine the psychosocial benefits and consequences of medical student involvement in prior disasters and developing attitudes in light of the coronavirus disease 2019 pandemic. We conclude by offering our thoughts on medical student involvement in future disasters.

The Silver Lining: Advances in the Surgical Management of Brain Trauma Attributable to War.

Within the text we elaborate on the relationship between war and medicine, particularly as it pertains to neurosurgery and the management of brain trauma, and emphasize neurosurgical advancements in the treatment of brain trauma gleaned from U.S.-involved conflicts of the 21st century.

Subcutaneous Administration of Angiotensin-(1-7) Improves Recovery after Traumatic Brain Injury in Mice.

Angiotensin II (Ang II)-mediated activation of its type I receptor (AT1R) in the central nervous system promotes glial proliferation, local inflammation, and a decrease of cerebral blood flow. Angiotensin-(1-7) (Ang-(1-7))-an Ang II derivative peptide-signals through the Mas receptor (MasR) in opposition to Ang II/AT1R, promoting anti-inflammatory, vasodilatory, and neuroprotective effects. As our laboratory has previously demonstrated beneficial effects of AT1R inhibition following controlled cortical impact (CCI) in mice, we asked whether activation of Ang-(1-7)/MasR signaling would also be beneficial in this model. Adult male C57BL/6 mice were injured by CCI. Ang-(1-7) or vehicle was administered subcutaneously (S.Q.) at 1 mg/kg/day at 1 or 6 h post-injury, until animals were sacrificed at 3 or 29 days post-injury (dpi). Ang-(1-7) attenuated motor deficits at 3 dpi and improved performance in the Morris Water Maze at 28 dpi. Brain histology or magnetic resonance imaging (MRI) indicated that Ang-(1-7)-treated mice had smaller lesion volumes at 3, 10, 24, and 29 dpi. Pre-treatment with A779, a MasR antagonist, prevented Ang-(1-7) from reducing lesion volume at 3 dpi, suggesting that the benefits of Ang-(1-7) were MasR-dependent. Immunohistochemistry revealed that Ang-(1-7) reduced microgliosis at 3 and 29 dpi, and astrogliosis at 29 dpi. Ang-(1-7) decreased neuronal and capillary loss at 29 dpi. In summary, S.Q. administration of Ang-(1-7) after injury had anti-inflammatory, neuroprotective, and cerebrovascular-protective actions leading to improved functional and pathological recovery in a mouse model of traumatic brain injury (TBI). These data show for the first time that Ang-(1-7) has potential therapeutic use for TBI.

Inadequate Decompressive Craniectomy Following a Wartime Traumatic Brain Injury - An Illustrative Case of Why Size Matters.

Traumatic brain injury has been called the "signature injury" of the wars in Iraq and Afghanistan, and the management of severe and penetrating brain injury has evolved considerably based on the experiences of military neurosurgeons. Current guidelines recommend that decompressive hemicraniectomy be performed with large, frontotemporoparietal bone flaps, but practice patterns vary markedly. The following case is illustrative of potential clinical courses, complications, and efforts to salvage inadequately-sized decompressive craniectomies performed for combat-related severe and penetrating brain injury. The authors follow this with a review of the current literature pertaining to decompressive craniectomy, and finally provide their recommendations for some of the technical nuances of performing decompressive hemicraniectomy after severe or penetrating brain injury.