The Clinical And Experimental Studies On Hypopituitarism Following Traumatic Brain Injury

There are two parts in our study. We study pituitary dysfunction and its significanceafter acute traumatic brain injury (TBI) from the view of clinical and animal experimentsrespectively. Each part of the study is summarized as follows:Part1: Pituitary dysfunction and its clinical significance in the patientsafter acute traumatic brain injuryObjective: To study the functional change of pituitary and its clinical significance inthe patients after acute TBI.Methods: Fifty five patients with acute TBI were randomly chosen as the observationgroup and fifteen health adults were chosen as the control group. The observation grouppatients were divided into mild group (13-15scores), medium group (9-12scores) andsevere group (3-8scores) according to glasgow coma scale (GCS) when they just arrivedthe hospital. At the same time, they were divided into mild shift group (less than5mm),medium shift group (between5and10mm), severe shift group (more than10mm)according to the degree of midline structures displacement and0-30ml group,31-60mlgroup, more than61ml group according to the cerebral hematoma volume. Test pituitaryhormones of adrenocorticotropic hormone (ACTH), cortisol (COR), triiodothyronine (T3),thyroxine (T4), thyroid-stimulating hormone (TSH), prolactin (PRL), follicle-stimulatinghormone (FSH), luteinizing hormone (LH) on the1th,3th,5th,7th,14th,30th day ofthe observation group and the1th day of the control group with chemiluminescence. Theobservation group patients were divided into the good group and the bad group accordingto the glasgow outcome score in the6th month after TBI. The relationship between thepituitary hormones levels and the severity of TBI as well as prognosis were statisticallyanalyzed. Results:(1) When compared with the control group, the levels of ACTH and COR ofobservation group were increased significantly, and the hormones levels of medium group,medium shift group,31～60ml group and good group raised significantly, the peaksappeared on the first and seventh day respectively. The difference between the two groupswas significant (P<0.05or0.01).(2) Both the T3and TSH levels of TBI patients weresignificantly lower when compared with the control group, the difference was significant(P<0.05or0.01). When the degree of the injury severity, midline structures displacement,hematoma volume, bad prognosis become worse, the hormones levels would reduce moreobviously and recover more slow.(3) The FSH and LH levels were significantly increasedon the first day after TBI(P<0.01). When the degree of the injury severity, midlinestructures displacement, hematoma volume, bad prognosis become worse, the hormoneslevels would increase more obviously, and they would recover three days later.(4) Therewas no difference between groups of the FSH and LH levels.Conclusion: The levels of ACTH, COR, FSH and LH in the acute phase of patientswith TBI were increased remarkably compared with that of the controls (P<0.01). However,the levels of T3and TSH were reduced remarkably (P<0.01). The variations of the pituitaryhormones levels were more obviously as the severity increased and the prognosis grownworse. The pituitary hormones levels of the mild TBI patients and the better prognosispatients were gradually recovered to normality. The basal volume and dynamic changes ofpituitary hormones in TBI patients can serve as a guideline for judging the injury degreeand prognosis.Part2: The clinical significance of the injury and functional change ofhypothalamic-pituitary-adrenal axis after acute severely traumatic braininjury in the ratsObjective: To study the clinical significance of the injury and functional change ofhypothalamic-pituitary-adrenal (HPA) axis after acute severe traumatic brain injury in theRats.Methods: Forty healthy male SD rats were divided into four groups with10each group on random: model group, sham group, treatment group, placebo group. The TBImodel was established by improved Feeney’s method, which uses a hammer of forty gramsweight falling from twenty five cm height to strike the rats brain. The rats of the shamgroup were only cut the scalp to open a bone window, but do not cause brain trauma. A lowdose of dexamethasone (0.6mg/kg) was injected into the abdominal cavity of the treatmentgroup rats at10th minute,24th hour and48th hour after TBI. The same dose of salinewas injected into the abdominal cavity of the placebo group rats at the same time. Gettingthe blood by the femoral vein and separating serum at four time points:3th hour,12thhour,24th hour and72th hour after TBI. The plasma corticosterone (CORT) andadrenocorticotropic hormone (ACTH) levels were measured by chemiluminescence. Allthe rats were injected ACTH (1μg) into the abdominal cavity at3th,24th, and72th hourafter TBI. Test CORT60th minute after the injection of ACTH once more and calculatethe variation of the CORT. The hypothalamic, pituitary and adrenal of the rats were takenout for observing pathological changes by HE staining and IL-6, TNF-α expressiondetecting by immunohistochemical techniques at72th hour after TBI. The data wasanalyzed by one-way AVNOA and SNK-q.Results:(1)The levels of ACTH and CORT on3th hour of model group raisedremarkably compared with that of the sham group, then they reduced gradually and raisedagain. The levels of CORT were lower than that of the sham group at every time pointsafter ACTH stimulation test and there is much significantly difference as time goes by(P<0.05or0.01). The levels of CORT at all time points of treatment group were changedremarkably compared with that of the placebo group. However, the ACTH levels oftreatment group on24h increased slightly than that of placebo group. And the tendency ofthem was similar to the model group (P<0.05or0.01).(2)The count of the cells of modelgroup nearby hypothalamic paraventricular nuclear reduced. The volume of cells becamesmaller, part of the neuron bodies became into the spindle or triangle, the nuclearcondensation, even the interior structure of the cell became ambiguous. The cellmorphology of adenohypophysis distal section of model group is still normal. However,the cells reduced in number and arranged irregularly in stucture. The count of the capillaries and connective tissue increased significantly. The number of the cells of thetreatment group didn’t decrease significantly, while the number of the capillaries andconnective tissue increased significantly. The obvious edema, the reduced number, thekaryopyknosis and the darker chromatin staining of all the rats adrenocortical cells didn’tbe observated.(3)The number of the hypothalamus and pituitary cells which express IL-6and TNF-α in the model group was more significantly increased when compared with thatin the sham group (P<0.01), while the number of this kind of cell in the treatment groupwas significantly decreased than that in the placebo group (P<0.01). The number of theadrenal cortex cells which express IL-6in the treatment group was more significantlydecreased when compared with that in the placebo group (P<0.01), while the number ofthis kind of cell in the model group was significantly increased than that in the sham group(P<0.01). However, there was no significant difference of the TNF-α between all thegroups (P>0.05).Conclusion: Functional change of adrenal occurs early in the severe acute traumaticbrain injury rats, and the response of adrenal to ACTH decreased as time goes by. Thepathological changes and the immune response of the hypothalamus and pituitary involvedin the changes of the HPA axis secretory function. Low-dose, short-course dexamethasonecan delay the pathological changes, reduce the inflammatory response of HPA axis andincrease the sensitivity of adrenal response to ACTH.