MERTK-related engulfment of norepinephrinergic neuronal presynaptic membrane by astrocytes following acute TBI and potentiation effect of peripheral nerve modulation

TBI triggered reactive astrogliosis in the LC, with elevated GFAP-Lamp2 colocalization. Increased GFAP-NET colocalization indicated astrocytic engulfment of presynaptic membrane proteins from norepinephrinergic neurons. Cell interaction analysis identified MERTK-mediated astrocyte-norepinephrinergic neuron crosstalk; GFAP-MERTK immunofluorescence confirmed spatially increased astrocytic MERTK expression linked to NET phagocytosis.

LF-PNM further enhanced astrocytic phagocytosis of LC norepinephrinergic presynaptic proteins after TBI, reduced neuronal apoptosis, facilitated neuronal activation, and rescued arousal and stress functions.</p> <p>After acute TBI, LC astrocytes phagocytose norepinephrinergic presynaptic proteins <i>via</i> MERTK. LF-PNM enhances this process, improving post-TBI arousal and stress dysfunction.</p> <p></p><p>Acute TBI induces extensive apoptosis of LC norepinephrinergic neurons and robust reactive activation of astrocytes, accompanied by markedly elevated astrocytic phagocytosis of norepinephrinergic presynaptic membranes via the MERTK-dependent pathway.</p><p>PNM exerts differential effects on LC norepinephrinergic neurons and astrocytes after acute TBI: LF-PNM suppresses neuronal apoptosis and further boosts astrocyte reactive activation and phagocytic activity, whereas HF-PNM hardly affects astrocyte activation yet impairs their phagocytic capacity.</p><p>Acute TBI causes deficits in arousal and stress functions, and PNM ameliorates these neurological impairments, with LF-PNM showing superior therapeutic efficacy.</p><p></p> <p>Acute TBI induces extensive apoptosis of LC norepinephrinergic neurons and robust reactive activation of astrocytes, accompanied by markedly elevated astrocytic phagocytosis of norepinephrinergic presynaptic membranes via the MERTK-dependent pathway.</p> <p>PNM exerts differential effects on LC norepinephrinergic neurons and astrocytes after acute TBI: LF-PNM suppresses neuronal apoptosis and further boosts astrocyte reactive activation and phagocytic activity, whereas HF-PNM hardly affects astrocyte activation yet impairs their phagocytic capacity.</p> <p>Acute TBI causes deficits in arousal and stress functions, and PNM ameliorates these neurological impairments, with LF-PNM showing superior therapeutic efficacy.</p>