Neuroprotective Effects of Dexmedetomidine against Glutamate Agonist-induced Neuronal Cell Death Are Related to Increased Astrocyte Brain-derived Neurotrophic Factor Expression

Degos, Vincent; Charpentier, Tifenn Le; Chhor, Vibol; Brissaud, Olivier; Lebon, Sophie; Schwendimann, Leslie; Bednareck, Nathalie; Passemard, Sandrine; Mantz, Jean; Gressèns, Pierre

doi:10.1097/aln.0b013e318286cf36

Cited by 144 publications

(102 citation statements)

References 40 publications

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“…In vitro and in vivo experimental models of adult (15,16) and perinatal brain injury (17)(18)(19)(20) have identified neuroprotective effects of DEX that are α-2A-dependent (19). For example, in adult rats given unilateral transient forebrain ischemia, the combination of DEX and hypothermia improved the short-term neurologic outcome compared to controls (21).…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine reduces cranial temperature in hypothermic neonatal rats

et al. 2015

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Background:The α2-adrenergic agonist dexmedetomidine (DEX) is increasingly used for prolonged sedation of critically ill neonates, but there are currently no data evaluating possible consequences of prolonged neonatal DEX exposure. We evaluated the pharmacokinetics and histological consequences of neonatal DEX exposure. Methods: DEX was administered (s.c.) to naive (uninjured) neonatal Lewis rats to provide acute (25 µg/kg, ×1) or prolonged (25 µg/kg three times daily, ×2 or ×4 d) exposure. Therapeutic hypothermia was simulated using a water-cooled blanket. Cranial temperatures were measured using an infrared thermometer. DEX concentrations were measured by LC-MS in plasma and homogenized brainstem tissue for pharmacokinetic analysis. Cortex, cerebellum, and brainstem were evaluated for evidence of inflammation or injury. results: Prolonged neonatal DEX exposure was not associated with renal or brain pathology or indices of gliosis, macrophage activation, or apoptosis in either hypothermic or control rats. Plasma and brain DEX concentrations were tightly correlated. DEX peaked within 15 min in brain and reduced cranial temperature from 32 to 30 °C within 30 min after injection in cooled rats. conclusion: Prolonged DEX treatment in neonatal rats was not associated with abnormal brain histology. These data provide reassuring preliminary results for using DEX with therapeutic hypothermia to treat near-term brain injury. i n critically ill neonates, pain-related stress affects developmental outcomes, so appropriate pain management is paramount (1). Opioid infusions, sometimes in combination with benzodiazepines, are commonly administered with the intent to decrease pain, agitation, and stress responses in neonates exposed to frequent procedures, during mechanical ventilation, or during therapeutic cooling for hypoxic-ischemic encephalopathy (HIE). However, opioid and benzodiazepine exposure may produce neuroapoptosis and neurodevelopmental abnormalities (2,3). To reduce opioid exposure, alternative pain medications are needed, but few of the analgesics used in adults have been tested in neonates. Dexmedetomidine (DEX) has recently become a popular analgesic used in adult critical care (4).A selective α-2 adrenoceptor agonist, DEX produces analgesic and sedative effects that can synergize with other analgesics (5,6). In randomized studies of adults, DEX lowers dosing requirements for adjunctive sedatives, shortens hospital stay, decreases psychosis, and may improve posthospitalization memory and cognitive function (7-9). It is recommended for short-term use only, less than 48 h. Minimal efficacy, pharmacokinetic, and safety data exist for neonates. Despite limited testing and without current Food and Drug Administration approval, the off-label use of DEX in pediatric and neonatal intensive care units is increasing (10-12). Since DEX can provide sedation and prevent shivering, it is a viable alternative to opioids for neonatal intensive care units patients undergoing therapeutic hypothermia as treatment for HIE. Con...

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine reduces cranial temperature in hypothermic neonatal rats

et al. 2015

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“…[11], [12] decreasing noxious stimuli evoked release of nociceptive substances, [13] and further interrupting the spinal neuron-glia cross talk and regulating the nociceptive transmission under chronic pain condition. [14] Thus, Dexmedetomidine might be an interesting adjuvant for neuraxial anesthesia and analgesia to decrease intra-and postoperative anesthetic consumption and prolong the postoperative analgesic duration, but the potentially increased risk of bradycardia, hypotension and neurotoxicity should be taken into consideration in clinical settings.…”

Section: Discussionmentioning

confidence: 99%

Effect of Diffe Rent Concentrations of Epidural D E Xmeditomidine for Post - Operative Analgesia

Raghupatruni¹,

Ganesh²

2015

jemds

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BACKGROUND:The aim of our study was to know the ideal epidural dose to achieve analgesia in the postoperative patients using different concentrations of epidural dexmeditomidine. METHODS AND MATERIALS: Ninety patients of either sex, with age ranging from 25 years to 60 years were randomly selected and divided into three groups of thirty each. Group A received epidural 0.25% bupivacaine along with 25mcg of dexmeditomidine, Group B received epidural 0.25% bupivacaine along with 50mcg dexmeditomidine and Group C received epidural 0.25% bupivacaine along with 75 mcg dexmeditomidine. The duration of analgesia, sedation and cardiovascular stability were studied. RESULTS: Analgesia and sedation was more in Group C than the other two groups. Cardiovascular stability was good in groups A and B.

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“…126 HyperDexmedetomidine is short-acting, provides mild to moderate sedation and analgesic effects, allows clinical assessment, and may be neuroprotective. 95 Dexmedetomidine, however, frequently causes hypotension and bradycardia.…”

Section: Glycemic Control In Pcasmentioning

confidence: 99%

Critical Care Management Focused on Optimizing Brain Function After Cardiac Arrest

Nakashima

Hifumi

Kawakita

et al. 2017

Circ J

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The discussion of neurocritical care management in post-cardiac arrest syndrome (PCAS) has generally focused on target values used for targeted temperature management (TTM). There has been less attention paid to target values for systemic and cerebral parameters to minimize secondary brain damage in PCAS. And the neurologic indications for TTM to produce a favorable neurologic outcome remain to be determined. Critical care management of PCAS patients is fundamental and essential for both cardiologists and general intensivists to improve neurologic outcome, because definitive therapy of PCAS includes both special management of the cause of cardiac arrest, such as coronary intervention to ischemic heart disease, and intensive management of the results of cardiac arrest, such as ventilation strategies to avoid brain ischemia. We reviewed the literature and the latest research about the following issues and propose practical care recommendations. Issues are (1) prediction of TTM candidate on admission, (2) cerebral blood flow and metabolism and target value of them, (3) seizure management using continuous electroencephalography, (4) target value of hemodynamic stabilization and its method, (5) management and analysis of respiration, (6) sedation and its monitoring, (7) shivering control and its monitoring, and (8) glucose management. We hope to establish standards of neurocritical care to optimize brain function and produce a favorable neurologic outcome.

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Neuroprotective Effects of Dexmedetomidine against Glutamate Agonist-induced Neuronal Cell Death Are Related to Increased Astrocyte Brain-derived Neurotrophic Factor Expression

Abstract: These results suggest that dexmedetomidine increased astrocyte expression of BDNF through an extracellular signal-regulated kinase-dependent pathway, inducing subsequent neuroprotective effects.

Cited by 144 publications

References 40 publications

Dexmedetomidine reduces cranial temperature in hypothermic neonatal rats

Dexmedetomidine reduces cranial temperature in hypothermic neonatal rats

Effect of Diffe Rent Concentrations of Epidural D E Xmeditomidine for Post - Operative Analgesia

Critical Care Management Focused on Optimizing Brain Function After Cardiac Arrest

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