natriuretic-peptide--brain and Brain-Injuries

Hemodynamic mechanism for brain edema forrmation in patients with hypertensive encephalopathy is unclear. Potential roles of natriuretic peptides in the pathogenesis of hypertensive encephalopathy are discussed. A 32-year-old man presented with slight left hemiparesis. He was slightly confused, and his blood pressure was extremely high. Cranial plain computerized tomography scans revealed diffuse brain edema mainly in the supratentorial white matter region. Blood examination revealed that plasma concentrations of atrial and brain natriuretic peptides were significantly high. His left hemiparesis disappeared within a day, but he tended to be agitated. His altered mental status, however, resolved with control of blood pressure. Serial magnetic resonance imagings demonstrated that the magnitude of brain edema was attenuated in proportion to decline in plasma concentrations of natriuretic peptides. This case suggests that significant elevation of plasma concentrations of natriuretic peptides may contribute to an acute rise in blood pressure, and that these peptides potentially play an important role in development of brain edema in hypertensive encephalopathy.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Brain; Brain Injuries; Humans; Hypertensive Encephalopathy; Magnetic Resonance Imaging; Male; Natriuretic Peptide, Brain; Obesity; Radiography; Renin-Angiotensin System; Time Factors

Ischemic stroke followed by cerebral artery occlusion is a main cause of chronic disability worldwide. Recombinant human brain natriuretic peptide (rhBNP) has been reported to alleviate sepsis-induced cognitive dysfunction and brain I/R injury. However, the function and molecular mechanisms of rhBNP in ischemic brain injury have not been clarified. For establishment of an animal model of ischemic brain injury, C57BL/6 mice were treated with middle cerebral artery occlusion (MCAO) surgery for 1 h and reperfusion for 24 h. After subcutaneous injection of rhBNP into model mice, neurologic deficits were assessed by evaluating behavior of mice according to Longa scoring system, and TTC staining was utilized to determine the brain infarct size of mice. The levels of oxidative stress markers, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA), were detected in hippocampal tissues of mice by corresponding kits. Cell apoptosis in hippocampus tissues was examined by TUNEL staining. Protein levels of antioxidant enzymes (HO-1 and NQO1) in cerebral cortex, apoptotic markers (Bax, Bcl-2, and cleaved caspase), and PI3K/AKT pathway-associated factors in hippocampus were tested by western blot analysis. The results revealed that injection of rhBNP decreased neurologic deficit scores, the percent of brain water content, and infarct volume. Additionally, rhBNP downregulated MDA level, upregulated the levels of SOD, CAT, and GSH in hippocampus of mice, and increased protein levels of HO-1 and NQO1 in the cortex. Cell apoptosis in hippocampus tissues of model mice was inhibited by rhBNP which was shown as the reduced TUNEL-positive cells, the decreased Bax, cleaved caspase-3, and cleaved caspase-9 protein levels, and the enhanced Bcl-2 protein level. In addition, rhBNP treatment activated the PI3K/AKT signaling pathway and upregulated the protein levels of HO-1 and NRF2. Overall, rhBNP activates the PI3K/AKT/HO-1/NRF2 pathway to attenuate ischemic brain injury in mice after MCAO by suppression of cell apoptosis and oxidative stress.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Brain Injuries; Brain Ischemia; Humans; Infarction, Middle Cerebral Artery; Mice; Mice, Inbred C57BL; Natriuretic Peptide, Brain; NF-E2-Related Factor 2; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Reperfusion Injury; Superoxide Dismutase

The aim of this study was to examine cardiac dysfunction during the first 2 weeks after isolated traumatic brain injury and its association with in-hospital mortality.. Retrospective.. Level 1 regional trauma center.. Adult patients with severe traumatic brain injury.. After institutional review board approval, data from adult patients with isolated traumatic brain injury who underwent echocardiography during the first 2 weeks after traumatic brain injury between 2003 and 2010 were examined. Patients with preexisting cardiac disease were excluded. Clinical characteristics and echocardiogram reports were abstracted. Cardiac dysfunction was defined as left ventricular ejection fraction less than 50% or presence of regional wall motion abnormality.. None.. We examined data from 139 patients with isolated traumatic brain injury who underwent echocardiographic evaluation. Patients were 58 ± 20 years old, 66% were male patients, and 62.6% had subdural hematoma; admission Glasgow Coma Scale score was 3 ± 1 (3-15) and head Abbreviated Injury Scale was 4 ± 1 (2-5). Of this cohort, 22.3% had abnormal echocardiogram: reduced left ventricular ejection fraction was documented in 12% (left ventricular ejection fraction, 43% ± 8%) and 17.5% of patients had a regional wall motion abnormality. Hospital day 1 was the most common day of echocardiographic exam. Abnormal echocardiogram was independently associated with all cause in-hospital mortality (9.6 [2.3-40.2]; p = 0.002).. Cardiac dysfunction in the setting of isolated traumatic brain injury occurs and is associated with increased in-hospital mortality. This finding raises the question as to whether there are uncharted opportunities for a more timely recognition of cardiac dysfunction and subsequent optimization of the hemodynamic management of these patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain Injuries; Creatine Kinase, MB Form; Echocardiography; Female; Heart Diseases; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; Stroke Volume; Troponin I; Young Adult

The role of brain natriuretic peptide (BNP) after traumatic brain injury (TBI) remains unclear, and its relationship with hyponatremia is still controversial. The aim of this study is to investigate the secretion pattern of N-terminal (NT)-proBNP in patients with TBI and to assess the relationship between NT-proBNP, sodium balance, and intracranial pressure (ICP).. We measured serum NT-proBNP levels of 84 patients with isolated TBI on a daily basis from day 1 to day 14 after injury.. In average, the peak of BNP level was measured at 703.9 pg/mL±179.1 pg/mL on day 3 after injury, which was correlated to the severity of TBI. Among patients with severe TBI, plasma NT-proBNP concentrations in patients with hyponatremia were statistically higher than those without hyponatremia (p<0.05). In the hyponatremic group, the plasma NT-proBNP increased to a peak of 1001.16 pg/mL±131.52 pg/mL within 48 hours after injury and maintained at a high level for 3 days. In the normonatremic group, the plasma NT-proBNP reached a peak of 826.43 pg/mL±337.43 pg/mL on day 5 and quickly decreased thereafter. In addition, we found plasma NT-proBNP concentrations in patients with ICP>15 mm Hg were significantly higher than those in patients with ICP≤15 mm Hg (p<0.01).. This study provides evidence that BNP plasma concentrations increase rapidly after TBI. Plasma BNP concentrations are correlated with hyponatremia in severe TBI patients but not in mild and moderate TBI patients. Furthermore, patients with elevated ICP have a higher serum BNP level in first 4 days after injury.

Topics: Brain Injuries; Female; Humans; Hyponatremia; Intracranial Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Time Factors

There is emerging evidence to suggest that brain natriuretic peptide (BNP) is elevated after acute brain injury, and that it may play an adaptive role in recovery through augmentation of cerebral blood flow (CBF). Through a series of experiments, we tested the hypothesis that the administration of BNP after different acute mechanisms of central nervous system (CNS) injury could improve functional recovery by improving CBF. C57 wild-type mice were exposed to either pneumatic-induced closed traumatic brain injury (TBI) or collagenase-induced intracerebral hemorrhage (ICH). After injury, either nesiritide (hBNP) (8 microg/kg) or normal saline were administered via tail vein injection at 30 min and 4 h. The mice then underwent functional neurological testing via rotorod latency over the following 5 days and neurocognitive testing via Morris water maze testing on days 24-28. Cerebral blood flow (CBF) was assessed by laser Doppler from 25 to 90 min after injury. After ICH, mRNA polymerase chain reaction (PCR) and histochemical staining were performed during the acute injury phase (<24 h) to determine the effects on inflammation. Following TBI and ICH, administration of hBNP was associated with improved functional performance as assessed by rotorod and Morris water maze latencies (p < 0.01). CBF was increased (p < 0.05), and inflammatory markers (TNF-alpha and IL-6; p < 0.05), activated microglial (F4/80; p < 0.05), and neuronal degeneration (Fluoro-Jade B; p < 0.05) were reduced in mice receiving hBNP. hBNP improves neurological function in murine models of TBI and ICH, and was associated with enhanced CBF and downregulation of neuroinflammatory responses. hBNP may represent a novel therapeutic strategy after acute CNS injury.

Topics: Acute Disease; Animals; Brain; Brain Injuries; Cerebral Hemorrhage; Cerebrovascular Circulation; Cognition Disorders; Cytokines; Disease Models, Animal; Fluoresceins; Male; Maze Learning; Mice; Mice, Inbred C57BL; Natriuretic Agents; Natriuretic Peptide, Brain; Nerve Degeneration; Nerve Regeneration; Neuroprotective Agents; Organic Chemicals; Recovery of Function; RNA, Messenger; Time Factors; Treatment Outcome

To study any possible relation between hyponatremia following brain injury and the presence of cerebral salt-wasting syndrome (CSWS) or the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), and if vasopressin, brain natriuretic peptide (BNP) and aldosterone have a role in its mechanism.. Patients with brain injury admitted to the intensive care unit were included and had their BNP, aldosterone and vasopressin levels dosed on day 7.. Twenty six adult patients were included in the study. Nine (34.6%) had hyponatremia and presented with a negative water balance and higher values of urinary sodium, serum potassium and diuresis than patients with normonatremia. The serum levels of BNP, aldosterone, and vasopressin were normal and no relation was observed between plasma sodium and BNP, aldosterone or vasopressin.. The most likely cause of hyponatremia was CSWS and there was no correlation between BNP, aldosterone and vasopressin with serum sodium level.

Topics: Adolescent; Adult; Aldosterone; Brain Diseases, Metabolic; Brain Injuries; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Natriuretic Peptide, Brain; Vasopressins; Young Adult

Historically, hyponatremia in patients with varying brain diseases was termed cerebral salt wasting. Hyponatremia secondary to CSW was reported to be a distinct entity from SIADH, with the distinguishing feature of decreased extracellular fluid volume. Brain natriuretic peptide, a peptide with natriuretic, vasorelaxant, and aldosterone-inhibiting properties, was recently implicated in aneurysmal SAH patients with CSW. Here, we describe 2 cases of CSW in TBI patients with elevated BNP levels. This phenomenon has not been previously described.. Two patients with TBI and hyponatremia were subject to analysis. Central lines were placed to assess volume status. Levels of BNP were measured at the onset of hypertonic saline infusion. Electrocardiogram and cardiac enzyme studies were performed to assess cardiac function. Serial imaging was performed to assess the extent of brain injury.. These patients with TBI had findings consistent with CSW with elevated BNP levels in the setting of normal cardiac function. In both cases, a high BNP level was observed after declining plasma Na levels despite aggressive hypertonic saline infusion. High BNP levels may be associated with CSW. Further studies are necessary to establish a causative role for BNP in TBI-induced CSW.

Topics: Brain Injuries; Electrocardiography; Fatal Outcome; Glasgow Coma Scale; Humans; Hyponatremia; Male; Middle Aged; Natriuretic Peptide, Brain; Plasma Volume; Tomography, X-Ray Computed

Topics: Aldosterone; Brain Injuries; Critical Care; Diuresis; Humans; Hyponatremia; Natriuretic Peptide, Brain; Osmosis

Hyponatremia after traumatic brain injury (TBI) may influence neurological function and treatment. A causal relationship between elevated serum concentrations of Type B natriuretic peptide (BNP) and hyponatremia has been implied after subarachnoid hemorrhage and other neurosurgical disorders, although the source of BNP has not been identified. We evaluated if hyponatremia and increased BNP occur after TBI and if BNP is produced/released by the brain within 24 h after injury.. NT-proBNP was measured in concomitant jugular venous and arterial blood samples within 24 h after TBI. NT-proBNP was elevated in both samples in six patients (24%). One patient (4%) showed an increased jugular NT-proBNP concentration above a normal arterial concentration, suggesting a brain source. In the other 24 patients the difference between jugular and arterial NT-proBNP was not statistically significant. Hyponatremia (< or =136 mEq/l) also occurred in six patients (24%), but only two (8%) had both increased arterial NT-proBNP and hyponatremia. In both the urine sodium was slightly elevated above normal, but not statistically different from other patients. The difference in serum sodium between hypo- and normo-natremic groups was significant, but mean NT-proBNP and jugular:arterial NT-proBNP differences were not.. In this pilot study BNP is elevated within 24 h after TBI in some patients. However, it does not originate from the brain and increased NT-proBNP concentrations are not consistently associated with hyponatremia or increased urinary sodium loss.

Topics: Adolescent; Adult; Aged; Arteries; Brain; Brain Injuries; Female; Humans; Hyponatremia; Jugular Veins; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Sodium

Brain natriuretic peptide (BNP) is a potent natriuretic and vasodilator factor which, by its systemic effects, can decrease cerebral blood flow (CBF). In aneurysmal subarchnoid hemorrhage (aSAH), BNP plasma concentrations were found to be associated with hyponatremia and were progressively elevated in patients who eventually developed delayed ischemic deficit secondary to vasospasm. The purpose of the present study was to evaluate trends in BNP plasma concentrations during the acute phase following severe (traumatic brain injury) TBI.. BNP plasma concentration was evaluated in 30 patients with severe isolated head injury (GCS<8 on admission) in four time periods after the injury (period 1: days 1-2; period 2: days 4-5; period 3: days 7-8; period 4: days 10-11). All patients were monitored for ICP during the first week after the injury.. The initial BNP plasma concentrations (42+/-36.9 pg/ml) were 7.3 fold (p<0.01) higher in TBI patients as compared to the control group (5.78+/-1.90 pg/ml). BNP plasma concentrations were progressively elevated through days 7-8 after the injury in patients with diffused SAH as compared to patients with mild or no SAH (p<0.001) and in patients with elevated ICP as compared to patients without elevated ICP (p<0.001). Furthermore, trends in BNP plasma concentrations were significantly and positively associated with poor outcome.. BNP plasma concentrations are elevated shortly after head injury and are continuously elevated during the acute phase in patients with more extensive SAH and in those with elevated ICP, and correlate with poor outcomes. Further studies should be undertaken to evaluate the role of BNP in TBI pathophysiology.

Topics: Adolescent; Adult; Brain Injuries; Female; Follow-Up Studies; Glasgow Coma Scale; Glasgow Outcome Scale; Humans; Intracranial Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Time Factors; Treatment Outcome

Outcome of patients suffering from traumatic brain injury (TBI) depends on the development of secondary brain damage. In this context, recent studies underlined the role of the natriuretic peptides- atrial natriuretic peptide and brain natriuretic peptide (BNP)-in aneurysmatic subarachnoidal hemorrhage (SAH). Especially BNP correlates with intracranial pressure and clinical outcome after SAH. Since its role in TBI remains unclear, the intracranial and systemic concentrations of N-terminal (NT)-proBNP were analyzed in patients suffering from severe TBI. We measured NT-proBNP levels in cerebrospinal fluid (CSF) and serum of 14 patients suffering from severe TBI (GCS15 mm Hg (n=6), the serum (800+/-150 pg/mL) and CSF levels (55+/-9 pg/mL) of NT-proBNP were significantly increased after 24 h, as compared to patients with ICP15 mm Hg. Further studies are currently performed to elucidate the physiologic role of NT-proBNP in TBI.

Topics: Adult; Aged; Aged, 80 and over; Blood-Brain Barrier; Brain Injuries; Female; Glasgow Outcome Scale; Humans; Intracranial Pressure; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Tomography, X-Ray Computed