Genes in TBI /Cytokines/pathophysiology of TBI at gene level!

NOTCH1
Hes1
FGF2
NMDA
ERK 1&2
NF-kB
P38
Nerf-1,2
CXCL4
CCR3,4
NADP
VRAC
Brd-U
PSA-NCAM
SOX9
DAPT
MAPK
TNF
TGF-alpha
RANTES
CRE
Wnt1

Once the TBI's injury occurs, data has shown that the size of the lesion is dependent not only on the extent and force of the trauma, but also on amount of  subsequent reactive inflammatory and anoxic event that follow the trauma.  Also the baseline level Activity of the Notch prior to the event is critical in minimizing the incoming effects of the trauma.  As upregulation of the Notch sometime pre-exists in some Nerve cells such as the one in the Retinal cells.  Here such upregulation seems to contribute to allowing de-differentiation proning cell to proliferation. Whether MEK is involved is beside the point, This influence of the Notch seems overall Neuroprotective when it comes to resisting inflammatory reactions.
The force of the Trauma cannot be neglected as it can cause a commotion stretching or changing the axial diameter of the cell sufficiently to induce stress and the c-JUN pathways,  but it can also be sectional, directly killing the pre-synaptic Neuron.  Such a section will disturb profoundly events occurring at the presynaptic membrane with pertubation and release of multiple preexcitatory Glutamate and the like, potentially inducing seizures in the TBI victims.  Evidences suggest, TBI inducing such a trauma induced section of the presynaptic neuron, will impact post synaptic events not only by lack of normal stimulation, a preliminary event to Anoikis of the post synaptic Neuron, but also use free NMDA receptors to potentiate Anoxic events into production of powerful toxic free radical and Oxidant beyond Nitric Oxide.  Without an sufficient upregulation of both the Nrf2 and the Nicotinamid (NAD) systems, the targeted Neuron is at risk of dying more likey through the Caspase 1 pathway.   Anoikis kills more likely through the Caspase 3 apoptotic pathway!
The Anoxia described above is evidently more severe if vascular section resulted from the trauma directly, however vascular compression coming from swelling of the brain tissue may achieve the same Anoxia.  Stimulation of the VRAC by various liberated toxic Peptides may affects ions (including Calcium) channels, leading to significant edema.  It is proposed that Tamoxifen may dampen this reaction and could be of use.  The purported effect of Tamoxifen could be Estrogen Receptor driven since there will more likely be upregulated under the effect of TNF and Interferon (cytokines) coming from inflammatory white cells called into the theater of the TBI.
Indeed, after a trauma that could potention section a blood vessel, or cause erosion of the endothelial surface, extracellular material such as Collagen will trigger Platelet derived events (PDGFR and PDGF) which will also, through CXCL/CCR3 or 4 trigger Macrophage attraction.  The macrophages in turn will expand the reaction by calling T-cells (and this recruitment is worsen by IL1 through its integrin action at Endothelial level) but also secrete several cytokine including TGF alpha which could activate both the MAPK pathways (that upregulate NOTCH dampens) or the PI3K/AKT pathways
leading to downstream Oxidative events that may expand into the CRE/MTOR paricularly if stress-c-JUN-NF-kB are in play.  This cycle will lead to NADH, Free radicals  That could only be Dampened by the involvement of the Nerf (s) and the Sirtuins and their activators (the Buteins).
And there you have it Buteins are Neuroprotective.  The MTOR inhibitors will be protective through the ctivation of c-AMP of course!