Biomechanism of resistance to retinal injury in woodpecker's eyes.

Retinal injury is the most common ocular impairment associated with shaken baby syndrome (SBS), which could lead to vision loss and blindness. However, a woodpecker does not develop retinal hemorrhages or detachment even at a high acceleration of 1,000×g during pecking. To understand the mechanism of retinal injury and its resistance strategy, we put insight into the special ability of the woodpecker to protect the retina against damage under acceleration-deceleration impact. In this study, the structural and mechanical differences on the eyes of the woodpecker and human were analyzed quantitatively based on anatomical observation. We developed finite element eye models of the woodpecker and human to evaluate the dynamic response of the retina to the shaking load obtained from experimental data. Moreover, several structural parameters and mechanical conditions were exchanged between the woodpecker and human to evaluate their effects on retinal injury in SBS. The simulation results indicated that scleral ossification, lack of vitreoretinal attachment, and rotational acceleration-deceleration impact loading in a woodpecker contribute to the resistance to retinal injuries during pecking. The above mentioned special physical structures and mechanical behavior can distribute the high strain in the posterior segment of the woodpecker's retina, which decrease the risk of retinal injury to SBS.

Neonatal shaking brain injury changes psychological stress-induced neuronal activity in adult male rats.

Neonatal shaking brain injury (SBI) leads to increases in anxiety-like behavior and altered hormonal responses to psychological stressors as adults. These abnormalities are hypothesized to be due to a change in sensitization in neuronal circuits as a consequence of neonatal SBI. We examined the effects of neonatal SBI on neuronal activity in the anxiety- and/or stress-related areas of adult rats using Fos immunohistochemistry. Exposure to a novel elevated plus maze (EPM) resulted in a marked increase in Fos expression in the parvocellular (PVNp) and magnocellular parts of the paraventricular nucleus and the ventral part of the bed nucleus of the stria terminalis (vBNST) of shaken rats (S group) compared to non-shaken control rats (C group). On the contrary, Fos expression was significantly lower in the medial nucleus of the amygdala and the ventral subiculum (vS) of S group rats than C group rats exposed to EPM. Although we found no significant correlation in the number of Fos-expressing cells in the vBNST and PVNp in the C group rats, these numbers were significantly correlated in the S group rats. Furthermore, in the S group rats, but not in the C group rats, the number of Fos-expressing cells in the vBNST was inversely correlated with that in the vS. Interestingly, previous neuronal tracing studies have demonstrated direct projections from the vS to the vBNST and from the vBNST to the PVNp. The present data suggest that neonatal SBI can alter neuronal activity in anxiety- and/or stress-related neuronal circuits.

Retroocular and Subdural Hemorrhage or Hemosiderin Deposits in Pediatric Autopsies.

The presence of hemosiderin in the optic nerve sheath and/or retina is sometimes used to estimate the timing of injury in infants or children with suspected non-accidental head trauma. To determine the prevalence of hemosiderin in deaths not associated with trauma, we performed a prospective study of retroocular orbital tissue, cranial convexity, and cervical spinal cord dura mater in infants and children <2.5 years age. In 53 cases of non-traumatic death, approximately 70% had blood or hemosiderin within the orbital fat, ocular muscles, and parasagittal cranial and/or cervical spinal subdural compartment. This bleeding is likely a consequence of the birth process. None had evidence of hemorrhage within the optic nerve sheath. Premature birth was less likely associated with orbital tissue hemorrhage. Caesarean section birth (mainly nonelective) was not associated with lower prevalence. Residual hemosiderin was identifiable up to 36 weeks postnatal age, suggesting gradual disappearance after birth. Cardiopulmonary resuscitation (performed in the majority of cases) was not associated with acute hemorrhage. In 9 traumatic deaths, 6 had blood and/or hemosiderin within the optic nerve sheath. Knowledge of the potential presence and resolution of hemosiderin in these locations is important for medicolegal interpretation of childhood deaths associated with head or brain injury.

Pattern of cerebrospinal immediate early gene c-fos expression in an ovine model of non-accidental head injury.

Expression of the immediate early gene, c-fos, was examined in a large animal model of non-accidental head injury ("shaken baby syndrome"). Lambs were used because they have a relatively large gyrencephalic brain and weak neck muscles resembling a human infant. Neonatal lambs were manually shaken in a manner similar to that believed to occur with most abused human infants, but there was no head impact. The most striking c-fos expression was in meningothelial cells of the cranial cervical spinal cord and, to a lesser degree, in hemispheric, cerebellar, and brainstem meninges. Vascular endothelial cells also frequently showed c-fos immunopositivity in the meninges and hemispheric white matter. It was hypothesised that this c-fos immunoreactivity was due to mechanical stress induced by shaking, with differential movement of different craniospinal components.

Diffuse neuronal perikaryal amyloid precursor protein immunoreactivity in an ovine model of non-accidental head injury (the shaken baby syndrome).

Non-accidental head injury ("shaken baby syndrome") is a major cause of death and disability in infants and young children, but it is uncertain whether shaking alone is sufficient to cause brain damage or an additional head impact is required. Accordingly, we used manual shaking in an ovine model in an attempt to answer this question since lambs have a relatively large gyrencephalic brain and weak neck muscles resembling a human infant. Neuronal perikaryal and axonal reactions were quantified 6 hours after shaking using amyloid precursor protein (APP) immunohistochemistry. Neuronal perikaryal APP was widely distributed in the brain and spinal cord, the first time such a diffuse neuronal stress response after shaking has been demonstrated, but axonal immunoreactivity was minimal and largely confined to the rostral cervical spinal cord at the site of maximal loading. No ischaemic-hypoxic damage was found in haematoxylin and eosin-stained sections.

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.

Delayed white matter injury in a murine model of shaken baby syndrome.

Shaken baby syndrome, a rotational acceleration injury, is most common between 3 and 6 months of age and causes death in about 10 to 40% of cases and permanent neurological abnormalities in survivors. We developed a mouse model of shaken baby syndrome to investigate the pathophysiological mechanisms underlying the brain damage. Eight-day-old mouse pups were shaken for 15 seconds on a rotating shaker. Animals were sacrificed at different ages after shaking and brains were processed for histology. In 31-day-old pups, mortality was 27%, and 75% of survivors had focal brain lesions consisting of hemorrhagic or cystic lesions of the periventricular white matter, corpus callosum, and brainstem and cerebellar white matter. Hemorrhagic lesions were evident from postnatal day 13, and cysts developed gradually between days 15 and 31. All shaken animals, with or without focal lesions, had thinning of the hemispheric white matter, which was significant on day 31 but not earlier. Fragmented DNA labeling revealed a significant increase in cell death in the periventricular white matter, on days 9 and 13. White matter damage was reduced by pre-treatment with the NMDA receptor antagonist MK-801. This study showed that shaking immature mice produced white matter injury mimicking several aspects of human shaken baby syndrome and provided evidence that excess release of glutamate plays a role in the pathophysiology of the lesions.