Age-Dependency of 45 Calcium Accumulation Following Lateral Fluid Percussion: Acute and Delayed Patterns

Previous studies from our laboratory have shown the neuroprotective potential of ketones after TBI in the juvenile brain. It is our premise that acutely after TBI, glucose may not be the optimum fuel and decreasing metabolism of glucose in the presence of an alternative substrate will improve cellular metabolism and recovery. The current study addresses whether TBI will induce age-related differences in the cerebral metabolic rates for glucose (CMRglc) after cortical controlled impact (CCI) and whether ketone metabolism will further decrease CMRglc after injury. Postnatal day 35 (PND35; n ¼ 48) and PND70 (n ¼ 42) rats were given either sham or CCI injury and placed on either a standard or a ketogenic (KG) diet. CMRglc studies using 14 C-2deoxy-d-glucose autoradiography were conducted on days 1, 3, or 7 post-injury. PND35 and PND70 standard-fed CCI-injured rats exhibited no significant neocortical differences in CMRglc magnitude or time course compared to controls. Measurement of contusion volume also indicated no age differences in response to TBI. However, PND35 subcortical structures showed earlier metabolic recovery compared to controls than PND70. Ketosis induced by the KG diet was shown to affect CMRglc in an age-dependent manner after TBI. The presence of ketones after injury further reduced CMRglc in PND35 and normalized CMRglc in PND70 rats at 7 days bilaterally after injury. The changes in CMRglc seen in PND35 TBI rats on the KG diet were associated with decreased contusion volume. These results suggest that conditions of reduced glucose utilization and increased alternative substrate metabolism may be preferable acutely after TBI in the younger rat.

Section: Age Differences In Cmrglc After Tbimentioning

confidence: 99%

The Effects of Age and Ketogenic Diet on Local Cerebral Metabolic Rates of Glucose After Controlled Cortical Impact Injury in Rats

Prins¹,

Hovda²

2009

“…Different motivational factors are involved in forced exercise compared to voluntary exercise (Leasure and Jones, 2008); thus it is predicted that the stress response will also differ. We utilized the fluid percussion injury (FPI) model for these studies, a type of TBI that in our hands results in no gross neuronal death (Gurkoff et al, 2006;Osteen et al, 2001). …”

Section: Introductionmentioning

confidence: 99%

Differential Effects of Voluntary and Forced Exercise on Stress Responses after Traumatic Brain Injury

Griesbach

Tio

Vincelli

et al. 2012

Voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF) after traumatic brain injury (TBI) when it occurs during a delayed time window. In contrast, acute post-TBI exercise does not increase BDNF. It is well known that increases in glucocorticoids suppress levels of BDNF. Moreover, recent work from our laboratory showed that there is a heightened stress response after fluid percussion injury (FPI). In order to determine if a heightened stress response is also observed with acute exercise, at post-injury days 0-4 and 7-11, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) release were measured in rats running voluntarily or exposed to two daily 20-min periods of forced running wheel exercise. Forced, but not voluntary exercise, continuously elevated CORT. ACTH levels were initially elevated with forced exercise, but decreased by post-injury day 7 in the control, but not the FPI animals. As previously reported, voluntary exercise did not increase BDNF in the FPI group as it did in the control animals. Forced exercise did not increase levels of BDNF in any group. It did, however, decrease hippocampal glucocorticoid receptors in the control group. The results suggest that exercise regimens with strong stress responses may not be beneficial during the early post-injury period.

“…3,[8][9][10][11][12][13][14][15][16][17][18][19] During the first four years of life, numerous cerebral developmental changes occur, which may contribute to these differences within the pediatric population, including continued myelination, changes in cerebrovascular tone, and increases in both brain size and neurotransmitter density. [20][21][22] Experimental studies of the age-dependent response to a scaled cortical impact found larger lesion volumes at seven days and one month post-TBI in four-week-old piglets, compared with five-dayold piglets.…”

mentioning

confidence: 99%

Influences of Developmental Age on the Resolution of Diffuse Traumatic Intracranial Hemorrhage and Axonal Injury

Weeks

Sullivan²,

Kilbaugh³

et al. 2014

This study investigated the age-dependent injury response of diffuse traumatic axonal injury (TAI) and regional subdural and subarachnoid intracranial hemorrhage (ICH) in two pediatric age groups using a porcine head injury model. Fifty-five 5-day-old and 40 four-week-old piglets-which developmentally correspond to infants and toddlers, respectivelyunderwent either a sham injury or a single rapid non-impact rotational injury in the sagittal plane and were grouped by post-TBI survival time (sham, 3-8 h, one day, 3-4 days, and 5-6 days). Both age groups exhibited similar initial levels of ICH and a significant reduction of ICH over time ( p < 0.0001). However, ICH took longer to resolve in the five-day-old age group. At 5-6 days post-injury, ICH in the cerebrum had returned to sham levels in the four-week-old piglets, while the five-day-olds still had significantly elevated cerebral ICH ( p = 0.012). Both ages also exhibited similar resolution of axonal injury with a peak in TAI at one day post-injury ( p < 0.03) and significantly elevated levels even at 5-6 days after the injury ( p < 0.008), which suggests a window of vulnerability to a second insult at one day post-injury that may extend for a prolonged period of time. However, five-day-old piglets had significantly more TAI than four-week-olds overall ( p = 0.016), which presents some evidence for an increased vulnerability to brain injury in this age group. These results provide insight into an optimal window for clinical intervention, the period of increased susceptibility to a second injury, and an age dependency in brain injury tolerance within the pediatric population.