Traumatic axonal injury is exacerbated following repetitive closed head injury in the neonatal pig.
Inflicted brain injury is associated with widespread traumatic axonal injury (TAI) and subdural hematoma and is the leading cause of death in infants and children. Anesthetized 3-5-day-old piglets were subjected to either a single (n = 5) or double (n = 6, 15 min apart) rapid (<15 msec), non-impact, axial rotations of the head. Peak rotational velocities (averaging 172 rad/sec for single and 138 rad/sec for double loads) were lower than those utilized to induce severe injuries (240-260 rad/sec; Raghupathi and Margulies, 2002). At 6 h post-injury, brains were evaluated for the presence TAI using immunohistochemistry for the 200-kDa neurofilament protein (NF200). Accumulation of NF200 was observed in both contiguous (swellings) and in disconnected axons (axon bulbs) predominantly in central deep and peripheral subcortical white matter regions in the frontal, temporal, and parietal lobes of all injured piglets. Although the density of injured axons did not significantly increase after two rotational loads, the distribution of injured axons shifted from a few foci (2.2 +/- 2.3 per animal) with 1-2 swellings/bulbs following a single rotation to significantly more foci (14.7 +/- 11.9), and additional foci (2.5 +/- 1.9) containing 3 or more axon swellings/bulbs following two rotational loads. The density and distribution of injured axons following a single mild rotation were significantly reduced compared with those obtained previously following a single more severe rotational load. Collectively, these data are indicative of the graded response of the immature brain to rotational load magnitude, and importantly, the vulnerability to repeated, mild, non-impact loading conditions.
Raghupathi
Ramesh
R
Department of Neurosurgery, University of Pennsylvania, Philadelphia, 19104, USA.
Mehr
Mehrdad F
MF
Helfaer
Mark A
MA
Margulies
Susan S
SS
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure; D001831:Body Temperature; D020833:Diffuse Axonal Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology*; D006339:Heart Rate; D012008:Recurrence; D038642:Shaken Baby Syndrome / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D013552:Swine; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology*