Apolipoprotein E Mimetic Peptide Increases Cerebral Glucose Uptake by Reducing Blood–Brain Barrier Disruption after Controlled Cortical Impact in Mice: An¹⁸F-Fluorodeoxyglucose PET/CT Study

Abstract

Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB) and reduces cerebral glucose uptake. Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI, and COG1410 has demonstrated neuroprotective activity in several models of TBI. However, the effects of COG1410 on VEGF and glucose metabolism following TBI are unknown. The current study aimed to investigate the expression of VEGF and glucose metabolism effects in C57BL/6J male mice subjected to experimental TBI. The results showed that controlled cortical impact (CCI)-induced vestibulomotor deficits were accompanied by increases in brain edema and the expression of VEGF, with a decrease in cerebral glucose uptake. COG1410 treatment significantly improved vestibulomotor deficits and glucose uptake and produced decreases in VEGF in the pericontusion and ipsilateral hemisphere of injury, as well as in brain edema and neuronal degeneration compared with the control group. These data support that COG1410 may have potential as an effective drug therapy for TBI.

LRP1 activation attenuates white matter injury by modulating microglial polarization through Shc1/PI3K/Akt pathway after subarachnoid hemorrhage in rats

“…Importantly, Bell et al showed that glial-secreted apoE3 and murine apoE, but not apoE4, could signal to surrounding cells via LRP1 [13]. COG1410 is a peptide derive from apoE amino acid residues 138–149 of the receptor region of apoE holoprotein with aminoisobutyric acid (Aib) substitutions at positions 140 and 145 (acetyl-AS-Aib-LRKL-Aib-KRLL-amide), which does not include the polymorphic residues at positions 112 and 158 that define the E2, E3, and E4 isoforms of apoE in humans [40]. Our data indicated that COG1410 promoted M2 microglial polarization after SAH.…”

Protein phosphatase 2A as a therapeutic target in inflammation and neurodegeneration

“…The possible involvement of PP2A in therapeutic effects of FTY720 has not been explored in these contexts. However, protective effects of PP2A-activating peptides have been demonstrated in experimental models of ischemic or physical brain injury (Cao et al, 2016; Hoane, Kaufman, Vitek, & McKenna, 2009; Kaufman et al, 2010; Laskowitz et al, 2012; Pang et al, 2017; Qin et al, 2017; Tukhovskaya, Yukin, Khokhlova, Murashev, & Vitek, 2009; Wu et al, 2016). In some of these studies, protection of neurological function was accompanied by prevention of BBB dysfunction (Cao et al, 2016; Pang et al, 2017; Qin, You, et al, 2017), suggesting at least some degree of overlap between therapeutic effects of FTY720 and PADs.…”

Apolipoprotein E-Mimetic Peptide COG1410 Enhances Retinal Ganglion Cell Survival by Attenuating Inflammation and Apoptosis Following TONI

“…ApoE not only participates in lipid metabolism but also exerts anti-inflammatory and anti-apoptotic effects via binding to its functional receptors (Pocivavsek et al, 2009). Our recent study revealed that the apoE-mimetic peptide COG1410 shows neuroprotective effects, characterized by anti-inflammation and anti-apoptosis, in mouse models of traumatic brain injury (TBI) and hemorrhagic stroke (Wu et al, 2016; Qin et al, 2017). However, the detailed role and mechanisms of COG1410 in RGCs protection and vision restoration after TONI are poorly understood.…”