Effects of dimeric PSD-95 inhibition on excitotoxic cell death and outcome after controlled cortical impact in rats: PSD-95 inhibition in experimental TBI

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Effects of dimeric PSD-95 inhibition on excitotoxic cell death and outcome after controlled cortical impact in rats : PSD-95 inhibition in experimental TBI. / Sommer, Jens Bak; Bach, Anders; Rytter, Hana Malá; Gynther, Mikko; Bjerre, Ann-Sofie; Gram, Marie Gajhede; Marschner, Linda; Strømgaard, Kristian; Mogensen, Jesper; Pickering, Darryl S.

In: Neurochemical Research, Vol. 42, No. 12, 2017, p. 3401-3413.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Sommer, JB, Bach, A, Rytter, HM, Gynther, M, Bjerre, A-S, Gram, MG, Marschner, L, Strømgaard, K, Mogensen, J & Pickering, DS 2017, 'Effects of dimeric PSD-95 inhibition on excitotoxic cell death and outcome after controlled cortical impact in rats: PSD-95 inhibition in experimental TBI', Neurochemical Research, vol. 42, no. 12, pp. 3401-3413. https://doi.org/10.1007/s11064-017-2381-y

APA

Sommer, J. B., Bach, A., Rytter, H. M., Gynther, M., Bjerre, A-S., Gram, M. G., Marschner, L., Strømgaard, K., Mogensen, J., & Pickering, D. S. (2017). Effects of dimeric PSD-95 inhibition on excitotoxic cell death and outcome after controlled cortical impact in rats: PSD-95 inhibition in experimental TBI. Neurochemical Research, 42(12), 3401-3413. https://doi.org/10.1007/s11064-017-2381-y

Vancouver

Sommer JB, Bach A, Rytter HM, Gynther M, Bjerre A-S, Gram MG et al. Effects of dimeric PSD-95 inhibition on excitotoxic cell death and outcome after controlled cortical impact in rats: PSD-95 inhibition in experimental TBI. Neurochemical Research. 2017;42(12):3401-3413. https://doi.org/10.1007/s11064-017-2381-y

Author

Sommer, Jens Bak ; Bach, Anders ; Rytter, Hana Malá ; Gynther, Mikko ; Bjerre, Ann-Sofie ; Gram, Marie Gajhede ; Marschner, Linda ; Strømgaard, Kristian ; Mogensen, Jesper ; Pickering, Darryl S. / Effects of dimeric PSD-95 inhibition on excitotoxic cell death and outcome after controlled cortical impact in rats : PSD-95 inhibition in experimental TBI. In: Neurochemical Research. 2017 ; Vol. 42, No. 12. pp. 3401-3413.

Bibtex

@article{91cda6e7b2f24a8f96388abb3170e0d1,
title = "Effects of dimeric PSD-95 inhibition on excitotoxic cell death and outcome after controlled cortical impact in rats: PSD-95 inhibition in experimental TBI",
abstract = "Therapeutic effects of PSD-95 inhibition have been demonstrated in numerous studies of stroke; however only few studies have assessed the effects of PSD-95 inhibitors in traumatic brain injury (TBI). As the pathophysiology of TBI partially overlaps with that of stroke, PSD-95 inhibition may also be an effective therapeutic strategy in TBI. The objectives of the present study were to assess the effects of a dimeric inhibitor of PSD-95, UCCB01-144, on excitotoxic cell death in vitro and outcome after experimental TBI in rats in vivo. In addition, the pharmacokinetic parameters of UCCB01-144 were investigated in order to assess uptake of the drug into the central nervous system of rats. After a controlled cortical impact rats were randomized to receive a single injection of either saline or two different doses of UCCB01-144 (10 or 20 mg/kg IV) immediately after injury. Spatial learning and memory were assessed in a water maze at two weeks post-trauma, and at four weeks lesion volumes were estimated. Overall, UCCB01-144 did not protect against NMDA-toxicity in neuronal cultures or experimental TBI in rats. Important factors that should be investigated further in future studies assessing the effects of PSD-95 inhibitors in TBI are discussed.",
author = "Sommer, {Jens Bak} and Anders Bach and Rytter, {Hana Mal{\'a}} and Mikko Gynther and Ann-Sofie Bjerre and Gram, {Marie Gajhede} and Linda Marschner and Kristian Str{\o}mgaard and Jesper Mogensen and Pickering, {Darryl S}",
year = "2017",
doi = "10.1007/s11064-017-2381-y",
language = "English",
volume = "42",
pages = "3401--3413",
journal = "Neurochemical Research",
issn = "0364-3190",
publisher = "Springer",
number = "12",

}

RIS

TY - JOUR

T1 - Effects of dimeric PSD-95 inhibition on excitotoxic cell death and outcome after controlled cortical impact in rats

T2 - PSD-95 inhibition in experimental TBI

AU - Sommer, Jens Bak

AU - Bach, Anders

AU - Rytter, Hana Malá

AU - Gynther, Mikko

AU - Bjerre, Ann-Sofie

AU - Gram, Marie Gajhede

AU - Marschner, Linda

AU - Strømgaard, Kristian

AU - Mogensen, Jesper

AU - Pickering, Darryl S

PY - 2017

Y1 - 2017

N2 - Therapeutic effects of PSD-95 inhibition have been demonstrated in numerous studies of stroke; however only few studies have assessed the effects of PSD-95 inhibitors in traumatic brain injury (TBI). As the pathophysiology of TBI partially overlaps with that of stroke, PSD-95 inhibition may also be an effective therapeutic strategy in TBI. The objectives of the present study were to assess the effects of a dimeric inhibitor of PSD-95, UCCB01-144, on excitotoxic cell death in vitro and outcome after experimental TBI in rats in vivo. In addition, the pharmacokinetic parameters of UCCB01-144 were investigated in order to assess uptake of the drug into the central nervous system of rats. After a controlled cortical impact rats were randomized to receive a single injection of either saline or two different doses of UCCB01-144 (10 or 20 mg/kg IV) immediately after injury. Spatial learning and memory were assessed in a water maze at two weeks post-trauma, and at four weeks lesion volumes were estimated. Overall, UCCB01-144 did not protect against NMDA-toxicity in neuronal cultures or experimental TBI in rats. Important factors that should be investigated further in future studies assessing the effects of PSD-95 inhibitors in TBI are discussed.

AB - Therapeutic effects of PSD-95 inhibition have been demonstrated in numerous studies of stroke; however only few studies have assessed the effects of PSD-95 inhibitors in traumatic brain injury (TBI). As the pathophysiology of TBI partially overlaps with that of stroke, PSD-95 inhibition may also be an effective therapeutic strategy in TBI. The objectives of the present study were to assess the effects of a dimeric inhibitor of PSD-95, UCCB01-144, on excitotoxic cell death in vitro and outcome after experimental TBI in rats in vivo. In addition, the pharmacokinetic parameters of UCCB01-144 were investigated in order to assess uptake of the drug into the central nervous system of rats. After a controlled cortical impact rats were randomized to receive a single injection of either saline or two different doses of UCCB01-144 (10 or 20 mg/kg IV) immediately after injury. Spatial learning and memory were assessed in a water maze at two weeks post-trauma, and at four weeks lesion volumes were estimated. Overall, UCCB01-144 did not protect against NMDA-toxicity in neuronal cultures or experimental TBI in rats. Important factors that should be investigated further in future studies assessing the effects of PSD-95 inhibitors in TBI are discussed.

U2 - 10.1007/s11064-017-2381-y

DO - 10.1007/s11064-017-2381-y

M3 - Journal article

C2 - 28828633

VL - 42

SP - 3401

EP - 3413

JO - Neurochemical Research

JF - Neurochemical Research

SN - 0364-3190

IS - 12

ER -

ID: 181908657