Dysphagia is a common complication following traumatic brain injury (TBI), and it is related to an increased risk of malnutrition, pneumonia, and poor prognosis. In this article, we present a case of TBI with persistent dysphagia treated with focal muscle vibration. A 100 Hz and 50 Hz vibratory stimuli were applied over the suprahyoid muscles and tongue (30 min twice a day; five days a week; for a total of four weeks) in addition to the conventional therapy to quickly recover swallowing and avoid the possibility of permanent deficits. In conclusion, this case highlights a novel therapeutic approach for persistent dysphagia in TBI, which should be considered in the management of dysphagia.

The human central nervous system (CNS) has a limited capacity for regeneration and repair, as many other organs do. Partly as a result, neurological diseases are the leading cause of medical burden globally. Most neurological disorders cannot be cured, and primary treatments focus on managing their symptoms and slowing down their progression. Cell therapy for neurological disorders offers several therapeutic potentials and provides hope for many patients. Here we provide a general overview of cell therapy in neurological disorders such as Parkinson\'s disease (PD), Alzheimer\'s disease (AD), amyotrophic lateral sclerosis (ALS), Wilson\'s disease (WD), stroke and traumatic brain injury (TBI), involving many forms of stem cells, including embryonic stem cells and induced pluripotent stem cells. We also address the current concerns and perspectives for the future. Most studies for cell therapy in neurological diseases are in the pre-clinical stage, and there is still a great need for further research to translate neural replacement and regenerative therapies into clinical settings.

Traumatic injuries of the brain and spinal cord are a significant source of mortality and long-term disability. A recent systematic study in a rat model of spinal cord injury (SCI) indicates severe, destructive, and very protracted inflammation as the key mechanism initiated by the massive injury involving the white matter. Although the severe inflammation is localized and counteracted by astrogliosis, it has a damaging effect on the blood vessels in the surrounding spinal cord, leading to persistent vasogenic edema. Evaluation of these injuries with imaging of the brain and spinal cord plays a crucial role in the acute trauma work-up, allowing clinicians to quickly identify abnormalities that require immediate medical or surgical intervention or to exclude them from the workup. Recently, anti-inflammatory agents have been shown to inhibit and accelerate the elimination of post-SCI inflammation in preclinical studies, and an exciting potential has arisen for the use of antiinflammatory drugs in clinical studies to achieve neuroprotection (i.e., inhibition of destruction caused by inflammation) and to inhibit vasogenic edema in SCI, traumatic brain injury, and stroke. In both subacute and chronic settings, imaging can guide therapy and provide important prognostic information. In this review, we discuss the imaging workup and evolving imaging findings of neurotrauma in the acute and chronic setting, including conventional and advanced imaging techniques. As neuroimaging is the primary mode of diagnostic analysis in neurotrauma, it is a critical component in future clinical trials evaluating neuroprotective therapies.

Traumatic Brain Injury is considered one of the most prevalent causes of death around the world; more than seventy millions of individuals sustain the condition per year. The consequences of traumatic brain injury on brain tissue are complex and multifactorial, hence, the current palliative treatments are limited to improve patients\' quality of life. The subsequent hemorrhage caused by trauma and the ongoing oxidative process generated by biochemical disturbances in the in the brain tissue may increase iron levels and reactive oxygen species. The relationship between oxidative damage and the traumatic brain injury is well known, for that reason, diminishing factors that potentiate the production of reactive oxygen species have a promissory therapeutic use. Iron chelators are molecules capable of scavenging the oxidative damage from the brain tissue and are currently in use for ironoverload- derived diseases. Here, we show an updated overview of the underlying mechanisms of the oxidative damage after traumatic brain injury. Later, we introduced the potential use of iron chelators as neuroprotective compounds for traumatic brain injury, highlighting the action mechanisms of iron chelators and their current clinical applications.

Cerebrovascular Diseases (CVD) comprise a wide spectrum of disorders, all sharing an acquired or inherited alteration of the cerebral vasculature. CVD have been associated with important changes in systemic and tissue Renin-Angiotensin System (RAS). The aim of this review was to summarize and to discuss recent findings related to the modulation of RAS components in CVD. The role of RAS axes is more extensively studied in experimentally induced stroke. By means of AT1 receptors in the brain, Ang II hampers cerebral blood flow and causes tissue ischemia, inflammation, oxidative stress, cell damage and apoptosis. On the other hand, Ang-(1-7) by stimulating Mas receptor promotes angiogenesis in brain tissue, decreases oxidative stress, neuroinflammation, and improves cognition, cerebral blood flow, neuronal survival, learning and memory. In regard to clinical studies, treatment with Angiotensin Converting Enzyme (ACE) inhibitors and AT1 receptor antagonists exerts preventive and therapeutic effects on stroke. Besides stroke, studies support a similar role of RAS molecules also in traumatic brain injury and cerebral aneurysm. The literature supports a beneficial role for the alternative RAS axis in CVD. Further studies are necessary to investigate the therapeutic potential of ACE2 activators and/or Mas receptor agonists in patients with CVD.

Traumatic brain injury (TBI) can cause disorders of consciousness (DOC) by impairing the neuronal circuits of the ascending reticular activating system (ARAS) structures, including the hypothalamus, which are responsible for the maintenance of the wakefulness and awareness. However, the effectiveness of drugs targeting ARAS activation is still inadequate, and novel therapeutic modalities are urgently needed.
The goal of this work is to describe the neural loops of wakefulness, and explain how these elements participate in DOC, with emphasis on the identification of potential new therapeutic options for DOC induced by TBI.
Hypothalamus has been identified as a sleep/wake center, and its anterior and posterior regions have diverse roles in the regulation of the sleep/wake function. In particular, the posterior hypothalamus (PH) possesses several types of neurons, including the orexin neurons in the lateral hypothalamus (LH) with widespread projections to other wakefulness-related regions of the brain. Orexins have been known to affect feeding and appetite, and recently their profound effect on sleep disorders and DOC has been identified. Orexin antagonists are used for the treatment of insomnia, and orexin agonists can be used for narcolepsy. Additionally, several studies demonstrated that the agonists of orexin might be effective in the treatment of DOC, providing novel therapeutic opportunities in this field.
The hypothalamic-centered orexin has been adopted as the point of entry into the system of consciousness control, and modulators of orexin signaling opened several therapeutic opportunities for the treatment of DOC.

Patients with acquired brain injury (ABI) suffer from cognitive deficits that interfere significantly with their daily lives. These deficits are long-lasting and no treatment options are available. A better understanding of the mechanistic basis for these cognitive deficits is needed to develop novel treatments. Intracellular cyclic adenosine monophosphate (cAMP) levels are decreased in ABI. Herein, we focus on augmentation of cAMP by PDE4 inhibitors and the potentially synergistic mechanisms in traumatic brain injury. A major acute pathophysiological event in ABI is the breakdown of the blood-brain-barrier (BBB). Intracellular cAMP pathways are involved in the subsequent emergence of edema, inflammation and hyperexcitability. We propose that PDE4 inhibitors such as roflumilast can improve cognition by modulation of the activity in the cAMPPhosphokinase A-Ras-related C3 botulinum toxin substrate (RAC1) inflammation pathway. In addition, PDE4 inhibitors can also directly enhance network plasticity and attenuate degenerative processes and cognitive dysfunction by increasing activity of the canonical cAMP/phosphokinase- A/cAMP Responsive Element Binding protein (cAMP/PKA/CREB) plasticity pathway. Doublecourtin and microtubule-associated protein 2 are generated following activation of the cAMP/PKA/CREB pathway and are decreased or even absent after injury. Both proteins are involved in neuronal plasticity and may consist of viable markers to track these processes. It is concluded that PDE4 inhibitors may consist of a novel class of drugs for the treatment of residual symptoms in ABI attenuating the pathophysiological consequences of a BBB breakdown by their anti-inflammatory actions via the cAMP/PKA/RAC1 pathway and by increasing synaptic plasticity via the cAMP/PKA/CREB pathway. Roflumilast improves cognition in young and elderly humans and would be an excellent candidate for a proof of concept study in ABI patients.

BACKGROUND: This study aimed to re-establish a Population Pharmacokinetic (PPK) model of oral phenytoin to further optimize the individualized medication regimen based on our previous research.
METHODS: Patients with intracranial malignant tumor requiring craniotomy were prospectively enrolled according to the inclusion criteria. Genotypes of CYP2C9*1 or *3 and CYP2C19*1, *2 or *3 were determined by real time PCR (TaqMan probe) method. Serum concentrations of phenytoin on the 4th and 7th day after oral administration were determined using fluorescence polarization immunoassay. The PPK parameters were estimated using Nonlinear Mixed Effects Models (NONMEM) and internal validation was performed using bootstraps. The predictive performance of the final model was evaluated by Normalized Predictive Distribution Errors (NPDEs) and diagnostic goodness- of-fit plots.
RESULTS: A total of 390 serum samples were collected from 170 patients in PPK model building group. The population typical values for Vm, Km and the apparent volume of distribution (V) in the final model were 17.5 mg/h, 6.41 mg/L and 54.8 L, respectively. Internal validation by bootstraps showed that the final model was stable and reliable. NPDEs with a normal distribution and a scatterplot with symmetrical distribution showed that the final model had good predictive capability. Individualized dose regimens of additional 40 patients in the external validation group were designed by the present final PPK model. The percentages of patients with serum concentrations within the therapeutic range were 61.53% (24/39) on the 4th day and 94.87% (37/39) on the 7th day, which were higher than the 39.33% (59/150) and 52.10% (87/167) of above 170 patients (P < 0.0001).
CONCLUSIONS: The present PPK final model for oral phenytoin may be used to further optimize phenytoin individualized dose regimen to prevent early seizure in patients after brain injury if patient characteristics meet those of the population studied.

Therapeutic hypothermia has consistently been shown to be a robust neuroprotectant in many labs studying different models of neurological disease. Although this therapy has shown great promise, there are still challenges at the clinical level that limit the ability to apply this routinely to each pathological condition. In order to overcome issues involved in hypothermia therapy, understanding of this attractive therapy is needed. We review methodological concerns surrounding therapeutic hypothermia, introduce the current status of therapeutic cooling in various acute brain insults, and review the literature surrounding the many underlying molecular mechanisms of hypothermic neuroprotection. Because recent work has shown that body temperature can be safely lowered using pharmacological approaches, this method may be an especially attractive option for many clinical applications. Since hypothermia can affect multiple aspects of brain pathophysiology, therapeutic hypothermia could also be considered a neuroprotection model in basic research, which would be used to identify potential therapeutic targets. We discuss how research in this area carries the potential to improve outcome from various acute neurological disorders.

Traumatic brain injury (TBI) is the main reason of lifelong disability and casualty worldwide. In the United State alone, 1.7 million traumatic events occur yearly, out of which 50,000 results in deaths. Injury to the brain could alter various biological signaling pathways such as excitotoxicity, ionic imbalance, oxidative stress, inflammation, and apoptosis which can result in various neurological disorders such as Psychosis, Depression, Alzheimer disease, Parkinson disease, etc. In literature, various reports have indicated the alteration of these pathways after traumatic brain injury but the exact mechanism is still unclear. Thus, in the first part of this article, we have tried to summarize TBI as a modulator of various neuronal signaling pathways. Currently, very few drugs are available in the market for the treatment of TBI and these drugs only provide the supportive care. Thus, in the second part of the article, based on TBI altered signaling pathways, we have tried to find out potential targets and promising therapeutic approaches in the treatment of TBI.