Brain Activity after Intermittent Hypoxic Brain Condition in Rats

Hypoxic brain injury is accompanied by a decrease in various functions. It is also known that obstructive sleep apnea (OSA) can cause hypoxic brain injury. This study aimed to produce a model of an intermittent hypoxic brain condition in rats and determine the activity of the brain according to the duration of hypoxic exposure. Forty male Sprague–Dawley rats were divided into four groups: the control group (n = 10), the 2 h per day hypoxia exposure group (n = 10), the 4 h per day hypoxia exposure group (n = 10), and the 8 h per day hypoxia exposure group (n = 10). All rats were exposed to a hypoxic chamber containing 10% oxygen for five days. Positron emission tomography–computed tomography (PET-CT) brain images were acquired using a preclinical PET-CT scanner to evaluate the activity of brain metabolism. All the rats were subjected to normal conditions. After five days, PET-CT was performed to evaluate the recovery of brain metabolism. Western blot analysis and immunohistochemistry were performed with vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). The mean SUV was elevated in the 2 h per day and 4 h per day groups, and all brain regions showed increased metabolism except the amygdala on the left side, the auditory cortex on the right side, the frontal association cortex on the right side, the parietal association cortex on the right side, and the somatosensory cortex on the right side immediately after hypoxic exposure. However, there was no difference between 5 days rest after hypoxic exposure and control group. Western blot analysis revealed the most significant immunoreactivity for VEGF in the 2, 4, and 8 h per day groups compared with the control group and quantification of VEGF immunohistochemistry showed more expression in 2 and 4 h per day groups compared with the control group. However, there was no significant difference in immunoreactivity for BDNF among the groups. The duration of exposure to hypoxia may affect the activity of the brain due to angiogenesis after intermittent hypoxic brain conditions in rats.

Atypical presentation of complex regional pain syndrome: neuropathic itching - A case report -

Background: In some patients with neuropathic pain (NP), such as complex regional pain syndrome (CRPS), itching rather than pain is the main symptom making diagnosis and treatment difficult.Case: We report a case of a 23-year-old man with a history of hypoxic brain damage who presented with pruritus of the left foot and ankle. His left foot was fractured, and he underwent surgery 6 months previously. After the operation and cast application, he developed uncontrolled pruritus, swelling, sweating, and flushing of the left foot skin with limping. On examination, he showed well-known features of CRPS without pain. He was diagnosed with an atypical CRPS with neuropathic itching (NI). With treatment modalities used for NP and CRPS, his pruritus subsided gradually, and the his ankle mobility improved.Conclusions: Unexplained itching can be the main symptom in some CRPS patients. Treatment according to NP can improve symptoms of NI in CRPS patients.

Intensive Care Management of Multiorgan Dysfunction and Hypoxic Brain Injury Secondary to Refractory Status Epilepticus

Refractory Status Epilepticus (RSE) is a medical emergency that may lead to permanent brain damage or death.Mortality rate is 16-39%. It is the life threatening condition in which continuous fits occur, despite treatmentwith benzodiazepines and one antiepileptic drug.A 25-year-old female, brought in emergency department with high-grade fever and frequent fits. GlasgowComa Scale (GCS) was 3/15 with unstable hemodynamics. Resuscitation started immediately and managed asstatus epilepticus. Patient was in multi organ failure on arrival. On the basis of history and examination, hypoxicbrain injury was diagnosed initially. Later on, refractory status epilepticus (RSE) with multi organ dysfunctionsyndrome (MODS) was diagnosed, after necessary investigations and treatment. Patient was managed as ateam with multidisciplinary approach and after continuous effort of 2 weeks, patient was successfullydischarged to home.

The Potential Role of Hypoxia-inducible Factor-1 in the Progression and Therapy of Central Nervous System Diseases

: Hypoxia-inducible factor-1 (HIF-1) is a heterodimer protein composed of an oxygen-regulated functional subunit, HIF-1α, and a structural subunit, HIF-1β, belonging to the basic helix-loop-helix family. Strict regulation of HIF-1 protein stability and subsequent transcriptional activity involves various molecular interactions and is primarily controlled by post-transcriptional modifications. Hypoxia, owing to impaired cerebral blood flow, has been implicated in a range of central nervous system (CNS) diseases by exerting a deleterious effect on brain function. As a master oxygen-sensitive transcription regulator, HIF-1 is responsible for upregulating a broad spectrum of target genes involved in glucose metabolism, angiogenesis, and erythropoiesis to generate the adaptive response to avoid or minimize hypoxic brain injury. However, prolonged, severe oxygen deprivation may directly contribute to the role-conversion of HIF-1, namely. From neuroprotection to the promotion of cell death. Currently, an increasing number of studies support the fact HIF-1 is involved in a variety of CNS-related diseases, such as intracranial atherosclerosis, stroke, and neurodegenerative diseases. This review article chiefly focuses on the effect of HIF-1 on the pathogenesis and mechanism of progression of numerous CNS-related disorders by mediating the expression of various downstream genes and extensive biological functional events. It presents robust evidence that HIF-1 may represent a potential therapeutic target for CNS-related diseases.

Repeated hypoxia exposure induces cognitive dysfunction, brain inflammation, and amyloidβ/p-Tau accumulation through reduced brain O-GlcNAcylation in zebrafish

Repetitive hypoxia (RH) exposure affects the initiation and progression of cognitive dysfunction, but little is known about the mechanisms of hypoxic brain damage. In this study, we show that sublethal RH increased anxiety, impaired learning and memory (L/M), and triggered downregulation of brain levels of glucose and several glucose metabolites in zebrafish, and that supplementation of glucose or glucosamine (GlcN) restored RH-induced L/M impairment. Fear conditioning (FC)-induced brain activation of and PKA/CREB signaling was abrogated by RH, and this effect was reversed by GlcN supplementation. RH was associated with decreased brain O-GlcNAcylation and an increased O-GlcNAcase (OGA) level. RH increased brain inflammation and p-Tau and amyloid β accumulation, and these effects were suppressed by GlcN. Our observations collectively suggest that changes in O-GlcNAc flux during hypoxic exposure could be an important causal factor for neurodegeneration, and that supplementation of the HBP/ O-GlcNAc flux may be a potential novel therapeutic or preventive target for addressing hypoxic brain damage.

Optimization of Hypoxic Brain Injuries Diagnostics in Full-Term Newborns

The problem of early diagnosis of the central nervous system damage in newborn before the onset of clinical symptoms remains relevant at the present time.The aim of the study was to optimize the hypoxic brain damage diagnosis in full-term newborns by analyzing the concentration of cytokines in the umbilical cord blood.Materials and methods. During the first stage of the study, a prospective analysis of concentrations of interleukins (IL-1β, IL-4, IL-6, IL-8, IL-10), TNF-α and neuron-specific enolase (NSE) in the umbilical cord blood serum of full-term newborns was performed. The second stage of the study included the retrospective analysis of clinical data and instrumental research methods. The main method for diagnosing in the development of hypoxic brain damage in newborns was neurosonography.Results. The development of hypoxic brain damage is evidenced by the concentration of IL-1β over 30.3 pg/ml, IL-4 – over 1.7 pg/ml, IL-6 – over 79.4 pg/ml, IL-8 – over 107.7 pg/ml, NSE – more than 10.3 ng/ml and TNF-α – more than 1.6 pg/ml in umbilical cord blood.Conclusion. The results of the study confirmed that the comprehensive assessment of the cytokines concentration in the umbilical cord blood improves the hypoxic brain damage diagnosis in newborns. Analysis of the level of these markers immediately after the birth will optimize the management tactics of newborns who have undergone hypoxic exposure in antenatal and intranatal period.