Delayed Hemispheric Neuronal Loss in Severely Head-Injured Patients

Abstract

Recent experimental studies have revealed that traumatic brain injury as well as ischemic brain injury can cause chronic progressive neuronal damage. In the present study, we demonstrate previously unreported delayed cerebral atrophy on computerized tomography (CT) scans in severely head-injured patients. Seventeen severely head-injured patients who required mild hypothermia to control intracranial hypertension after the failure of conventional therapies were retrospectively analyzed. All 17 patients survived more than 1 year. Delayed neuronal loss (DNL) was observed in only eight of the 17 patients. Eight patients with DNL required longer durations of mild hypothermia to control intracranial hypertension than nine patients without DNL. Six of these eight patients with DNL achieved functional recovery despite progressive atrophic changes demonstrated on CT scans. On CT scans, DNL was characterized by (1) the sudden appearance at several months postinjury of a low-density area in the hemisphere ipsilateral to the injury; (2) the preservation of essential cortical structure although related white matter structures showed severe atrophic changes; and (3) no spread of the low-density area to the contiguous territory of the other main cerebral artery. It is concluded that focal primary injury to underlying brain, if severe enough, can result in delayed hemispheric atrophy.

Caspase 7: increased expression and activation after traumatic brain injury in rats

“…It is also possible that caspase 7 was activated very early after TBI at statistically undetectable levels yet still cleaved caspase 12, akin to the previous report of Korfali et al (2004). It may then become engaged in a feedback loop that may be responsible, in part, for the continual loss of neurons that has been noted to occur over an extended period of time after TBI (Colicos et al 1996;Smith et al 1997;Conti et al 1998;Sato et al 2001;Shiozaki et al 2001). This low level feedback loop is suggested by findings that, while caspase 7 may become activated early in the apoptotic pathway, it peaks after caspase 12 and that it may be activated by active caspase 12 via caspase 9 (Rao et al 2001(Rao et al , 2002.…”

Major Depression Following Traumatic Brain Injury

“…Recent experimental studies of TBI suggest that diffuse neuronal damage and cell loss may progress over weeks to months after the initial insult in selectively vulnerable regions of the neocortex, hippocampus, thalamus, and striatum. [68][69][70] On the other hand, neuroimaging studies of patients with TBI have demonstrated delayed cerebral atrophy on computed tomographic scan and MR imaging, [71][72][73] as well as altered metabolic patterns consistent with neuronal loss and inflammation as evidenced by proton magnetic resonance spectroscopy. 74,75 Furthermore, behavioral outcome seems to be more strongly correlated with delayed rather than early imaging findings.…”

Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat

“…Axonal damage with widespread distribution, termed diffuse axonal injury (DAI), is an important contributor to the morbidity and mortality seen both clinically and in experimental TBI (Adams et al, 1989;Pierce et al, 1996;Maxwell et al, 1997;Christman et al, 1997), and is characterized by axonal swelling and, ultimately, disconnection. The intracellular DNA fragmentation that has been observed in white matter tracts of TBI patients for up to a year post-injury, may also contribute to continuing damage of the white matter tracts and be linked to the observed progressive atrophy with enlargement of the cerebral ventricles (Williams et al, 2001;Shiozaki et al, 2001). These observations of progressive brain atrophy have been replicated in experimental TBI models Pierce et al, 1998;Bramlett and Dietrich, 2002;Bramlett et al, 1997).…”