Neuroprotective properties of 5-HT1A receptor agonists En rodent models of focal and global cerebral ischemia

Prehn, Jochen H.M.; Backhauβ, Cord; Karkoutly, Chourouk; Nuglisch, Jörg; Peruche, Barbara; Roβberg, Christine; Krieglstein, Josef

doi:10.1016/0014-2999(91)90717-5

Cited by 81 publications

(27 citation statements)

References 42 publications

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“…This observation suggests that early 8-OH-DPAT treatment is producing its beneficial effects by acting on acute pathophysiological responses of TBI such as the attenuation of glutamate-induced excitotoxicity, which is known to occur early after TBI. 5-HT 1A receptor agonists reduce Na + influx [66], decrease glutamate release in experimental models of brain insult [15][16][17]62,79] and Parkinsons disease [69], and induce neuronal hyperpolarization [78]. Taken together, these data provide support for neuroprotection mediated by neuronal membrane hyperpolarization and increased resistance to glutamate-induced excitotoxicity.…”

Section: Discussionmentioning

confidence: 92%

“…Studies from our laboratory have demonstrated that the selective and high affinity 5-HT 1A receptor agonists repinotan HCL and 8-OH-DPAT enhance spatial learning and memory performance in a Morris water maze (MWM) task, reduce hippocampal neuron loss, and decrease cortical lesion size [50,54,55]. Beneficial effects of 5-HT 1A receptor agonists have also been reported in other models of CNS injury, such as focal or global cerebral ischemia [15][16][17]62,[78][79][80]87,94] and acute subdural hematoma [1].…”

Section: Introductionmentioning

confidence: 99%

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Acute treatment with the 5-HT1A receptor agonist 8-OH-DPAT and chronic environmental enrichment confer neurobehavioral benefit after experimental brain trauma

Kline

Wagner

Westergom

et al. 2007

Behavioural Brain Research

100

166

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Acute treatment with the 5-HT 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) or chronic environmental enrichment (EE) hasten behavioral recovery after experimental traumatic brain injury (TBI). The aim of this study was to determine if combining these interventions would confer additional benefit. Anesthetized adult male rats received either a cortical impact or sham injury followed 15 min later by a single intraperitoneal injection of 8-OH-DPAT (0.5 mg/kg) or saline vehicle (1.0 mL/kg) and then randomly assigned to either enriched or standard (STD) housing. Behavioral assessments were conducted utilizing established motor and cognitive tests on post-injury days 1-5 and 14-18, respectively. Hippocampal CA 1 /CA 3 neurons were quantified at 3 weeks. Both 8-OH-DPAT and EE attenuated CA 3 cell loss. 8-OH-DPAT enhanced spatial learning in a Morris water maze (MWM) as revealed by differences between the TBI+8-OH-DPAT+STD and TBI+VEHICLE+STD groups (P=0.0014). EE improved motor function as demonstrated by reduced time to traverse an elevated narrow beam in both the TBI+8-OH-DPAT+EE and TBI+VEHICLE +EE groups vs. the TBI+VEHICLE+STD group (P=0.0007 and P=0.0016, respectively). EE also facilitated MWM learning as evidenced by both the TBI+8-OH-DPAT+EE and TBI+VEHICLE+EE groups locating the escape platform quicker than the TBI+VEHICLE+STD group (P's<0.0001). MWM differences were also observed between the TBI+8-OH-DPAT+EE and TBI+8-OH-DPAT +STD groups (P=0.0004) suggesting that EE enhanced the effect of 8-OH-DPAT. However, there was no difference between the TBI+8-OH-DPAT+EE and TBI+VEHICLE+EE groups. These data replicate previous results from our laboratory showing that both a single systemic administration of 8-OH-DPAT and EE improve recovery after TBI and extend those findings by elucidating that the combination of treatments in this particular paradigm did not confer additional benefit. One explanation for the lack of an additive effect is that EE is a very effective treatment and thus there is very little room for 8-OH-DPAT to confer additional statistically significant improvement.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Acute treatment with the 5-HT1A receptor agonist 8-OH-DPAT and chronic environmental enrichment confer neurobehavioral benefit after experimental brain trauma

Kline

Wagner

Westergom

et al. 2007

Behavioural Brain Research

100

166

View full text Add to dashboard Cite

show abstract

“…Beneficial effects of 5-HT 1A -receptor agonists have also been reported in other models of central nervous system (CNS) injury, such as focal or global cerebral ischemia (De Vry and Jentzsch, 1998;De Vry et al, 1997Prehn et al, 1991Prehn et al, ,1993Semkova et al, 1998), and acute subdural hematoma (Alessandri et al, 1999). Thus, the aim of the current study was to determine whether the 5-HT 1A -receptor agonist buspirone (BUS) will also facilitate better neurobehavioral outcomes and attenuate histological damage after CCI injury.…”

Section: Introductionmentioning

confidence: 86%

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT_1A-Receptor Agonist Buspirone

Olsen

Sozda

Cheng

et al. 2012

Journal of Neurotrauma

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The aim of this study was to evaluate the potential efficacy of the serotonin 1A (5-HT 1A ) receptor agonist buspirone (BUS) on behavioral and histological outcome after traumatic brain injury (TBI). Ninety-six isofluraneanesthetized adult male rats were randomized to receive either a controlled cortical impact or sham injury, and then assigned to six TBI and six sham groups receiving one of five doses of BUS (0.01, 0.05, 0.1, 0.3, or 0.5 mg/kg) or saline vehicle (VEH, 1.0 mL/kg). Treatments began 24 h after surgery and were administered intraperitoneally once daily for 3 weeks. Motor function (beam-balance/beam-walk tests) and spatial learning/memory (Morris water maze) were assessed on post-operative days 1-5 and 14-19, respectively. Morphologically intact CA1/ CA3 cells and cortical lesion volume were quantified at 3 weeks. No differences were observed among the BUS and VEH sham groups in any end-point measure and thus the data were pooled. Regarding the TBI groups, repeated-measures ANOVAs revealed that the 0.3 mg/kg dose of BUS enhanced cognitive performance relative to VEH and the other BUS doses ( p < 0.05), but did not significantly impact motor function. Moreover, the same dose conferred selective histological protection as evidenced by smaller cortical lesions, but not greater CA1/ CA3 cell survival. No significant behavioral or histological differences were observed among the other BUS doses versus VEH. These data indicate that BUS has a narrow therapeutic dose response, and that 0.3 mg/kg is optimal for enhancing spatial learning and memory in this model of TBI. BUS may have potential as a novel pharmacotherapy for clinical TBI.

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“…Body temperature was maintained at 37°C by an infrared heating lamp during the surgical procedure. Afterwards, the animals were kept at an environmental temperature of 30°C for a period of 2 h in order to avoid cerebral hypothermia (Prehn et al, 1991). Rectal temperatures were controlled routinely.…”

Section: Focal Cerebral Ischemia In Micementioning

confidence: 99%

Transforming Growth Factor-β₁Prevents Glutamate Neurotoxicity in Rat Neocortical Cultures and Protects Mouse Neocortex from Ischemic Injury in vivo

Prehn

Backhauß

Krieglstein

1993

J Cereb Blood Flow Metab

Self Cite

223

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Transforming growth factor-β1 (TGF-β1) has been shown to be an injury-related peptide growth factor within the mammalian central nervous system. We tested whether TGF-β1 has the capacity to protect rat neocortical neurons against excitotoxic damage in vitro and mouse neocortex against ischemic injury in vivo. After 14 days in vitro, cultured neurons from rat cerebral cortex were exposed to 1 m M l-glutamate in serum-free culture medium. The cultures received TGF-β1 immediately after the addition of glutamate. Eighteen hours later, the cell viability of the cultures was determined using trypan blue exclusion. TGF-β1 (1–10 ng/ml) significantly reduced the excitotoxic neuronal damage in a concentration-dependent manner. In vivo, male NMRI mice were subjected to a permanent occlusion of the left middle cerebral artery by microbipolar electrocoagulation. After 48 h, the animals received a transcardiac injection of carbon black. The area of ischemia (devoid of carbon) was restricted to the neocortex and its size was determined planimetrically by means of an image-analyzing system. The treatment with TGF-β1 (1 μg/kg i.c.v.) at 6, 4, or 2 h prior to vessel occlusion reduced the area of ischemia by 5.3, 10.0, and 9.6%, respectively. The effect of the treatment with TGF-β1 was statistically significant (p < 0.05 by two-way ANOVA). The present in vitro and in vivo data suggest that TGF-β1 has the capacity to diminish the deleterious consequences of an excitotoxic or ischemic insult.

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Neuroprotective properties of 5-HT1A receptor agonists En rodent models of focal and global cerebral ischemia

Cited by 81 publications

References 42 publications

Acute treatment with the 5-HT1A receptor agonist 8-OH-DPAT and chronic environmental enrichment confer neurobehavioral benefit after experimental brain trauma

Acute treatment with the 5-HT1A receptor agonist 8-OH-DPAT and chronic environmental enrichment confer neurobehavioral benefit after experimental brain trauma

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT_1A-Receptor Agonist Buspirone

Transforming Growth Factor-β₁Prevents Glutamate Neurotoxicity in Rat Neocortical Cultures and Protects Mouse Neocortex from Ischemic Injury in vivo

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Neuroprotective properties of 5-HT1A receptor agonists En rodent models of focal and global cerebral ischemia

Cited by 81 publications

References 42 publications

Acute treatment with the 5-HT1A receptor agonist 8-OH-DPAT and chronic environmental enrichment confer neurobehavioral benefit after experimental brain trauma

Acute treatment with the 5-HT1A receptor agonist 8-OH-DPAT and chronic environmental enrichment confer neurobehavioral benefit after experimental brain trauma

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT1A-Receptor Agonist Buspirone

Transforming Growth Factor-β1Prevents Glutamate Neurotoxicity in Rat Neocortical Cultures and Protects Mouse Neocortex from Ischemic Injury in vivo

Contact Info

Product

Resources

About

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT_1A-Receptor Agonist Buspirone

Transforming Growth Factor-β₁Prevents Glutamate Neurotoxicity in Rat Neocortical Cultures and Protects Mouse Neocortex from Ischemic Injury in vivo