Raw Western blots data to assess cold shock protein expression

Preclinical and clinical studies show that mild to moderate hypothermia is
neuroprotective in sudden cardiac arrest, ischemic stroke, perinatal
hypoxia/ischemia, traumatic brain injury and seizures. Induction of
hypothermia largely involves physical cooling therapies, which induce
several clinical complications, while some molecules have shown to be
efficient in pharmacologically-induced hypothermia (PIH). Neurotensin
(NT), a 13 amino-acid neuropeptide that regulates body temperature,
interacts with various receptors to mediate its peripheral and central
effects. NT induces PIH when administered intracerebrally. However, these
effects are not observed if NT is administered peripherally, due to its
rapid degradation and poor passage of the blood brain barrier (BBB). We
conjugated NT to peptides that bind the low-density lipoprotein receptor
(LDLR) to generate “vectorized” forms of NT with enhanced BBB
permeability. We evaluated their effects in epileptic conditions following
peripheral administration. One of these conjugates, VH-N412, displayed
improved stability, binding potential to both the LDLR and NTSR-1,
rodent/human cross-reactivity and improved brain distribution. In a mouse
model of kainate (KA)-induced status epilepticus (SE), VH-N412 elicited
rapid hypothermia associated with anticonvulsant effects, potent
neuroprotection and reduced hippocampal inflammation. VH-N412 also reduced
sprouting of the dentate gyrus mossy fibers and preserved learning and
memory skills in the treated mice. In cultured hippocampal neurons,
VH-N412 displayed temperature-independent neuroprotective properties. To
the best of our knowledge, this is the first report describing the
successful treatment of SE with PIH. In all, our results show that
vectorized NT may elicit different neuroprotection mechanisms mediated
either by hypothermia and/or by intrinsic neuroprotective properties.