The Influence of Different Factors on Brain Weight

Objective To evaluate the neuroprotective effects of erythropoiet (EPO) for traumatic brain injury (TBI) in rats and investigate the possible role of endoplasmic reticullum stress response and Caspase-12-induced apoptosis. Methods According to the random number table, 140 male Sprague-Dawley rats were divided into sham injury group, sham injury plus EPO group, TBI group and TBI plus EPO group, with 35 rats per group. TBI was induced by a fluid percussion device. EPO (5 000 U/kg in saline) was administered intraperitoneally at 6 hours after injury. The rate of TUNEL positive cells in injured cortex were measured to evaluate cell apoptosis status. Neurological function was assessed at days 1, 4, 7, 21, 28 and 35 after intervention using a modified neurological severity score (mNSS). At 24 hours after injury, the expressions of Caspase-12 in injured cortex and C/EBP-homologous protein (CHOP) which was the symbol of ERS response were measured by Western blot and immunofluorescent staining to assess the changes of ERS response after TBI and EPO treatment. Results TUNEL-positive staining cell density was significantly increased by (30.3±2.3)% in the injured cortex 24 hours after injury (P<0.01). Compared with TBI group, TBI plus EPO group had a significant decrease of the positive rate of TUNEL cells [ (14.6±1.5)%] (P<0.01). Compared with TBI group, mNSS score significantly was decreased in TBI plus EPO group at 7-35 days after injury (P<0.05). At 24 hours after injury, the results of Western blot showed that the expression levels of Caspase-12 and CHOP in the injured cortex in TBI group were higher than those in sham group, but that in TBI plus EPO group was lower than those in TBI group (P<0.01). At 24 hours after injury, the results of immunofluorescent staining showed the rates of Caspase-12 and CHOP positive cells in the injured cortex in TBI group were higher than sham group (P<0.01). But the rates of Caspase-12 and CHOP positive cells in TBI plus EPO group was lower than that in TBI Group (P<0.01). Conclusion Exogenous EPO has significant neuroprotective effects on TBI rats. EPO may exert its neuroproective effects through suppression of ERS response and inhibition of Caspase-12-induced apoptosis. Key words: Brain injuries; Erythropoietin; Endoplasmic reticulum stress

要旨【目的】小児頭部外傷に対する大規模CT適応基準は，外傷性脳損傷（TBI）の発見を目的としており，頭蓋骨単独骨折（ISF）は見落とされる可能性がある。このため，本研究では2歳未満児のTBIとISFの危険因子を比較するため検討を行った。【対象】2013–2015年の3年間に頭部外傷で救急受診し，CTが施行された2歳未満児416例を後方視的に検討した。対象症例をTBI群：25例，ISF群：30例，異常所見なし群（以下NAF群）：361例の3群に分け特徴を比較した。また多変量解析でTBIとISFの危険因子を検討した。【結果】年齢は，TBI群は0–3か月で，ISF群は6–12か月で，NAF群は12か月以降で多かった。受傷機転は，ISF群で墜落が多く，TBI群では抱っこでの転倒・受傷機転不明が多かった。TBI群・ISF群ともに前頭部以外の皮下血腫がNAF群より多く，径も大きかった。多変量解析では，TBIと関連する因子は低年齢，受傷機転不明，2回以上の嘔吐，痙攣，前頭部以外の皮下血腫であったが，ISFと関連する因子は，経過時間（24時間以降または不明），前頭部以外の皮下血腫，5cm以上の皮下血腫であった。【結語】乳児頭部外傷におけるTBIとISFの危険因子は異なり，大規模基準で低リスクであってもISFを疑う場合は，経過観察もしくはCTが必要である。

Objective To investigate the effect of Ghrelin on gastrointestinal motility after traumatic brain injury (TBI). Methods A total of 72 adult male SD rats were randomly divided into sham operation group (n=8), TBI group (n=32) and Ghrelin group (n=32), according to the random number table. In the sham operation group, the scalp was sutured after craniotomy and sterilization, without any strike. In the TBI group, after intraperitoneal anesthesia, the skull was opened and the electric cortical contusion impactor was used to strike the center of bone window at the depth of 3 mm and the rate of 5 m/s. The duration of hitting the lowest point was 200 ms. In the Ghrelin group, 20 μg/kg of Ghrelin was injected into the rat via the tail vein 30 minutes after injury. The modified neurologicalseverity score (mNSS), percentage of water content in feces and percentage of gastric contents in body weight at 6, 24, 48 and 72 hours after operation in each group were measured. The stomach, the small intestine 15 cm from ileocecal junction, ileocecal junction (about 3 cm in the proximal ileal loops, about 3 cm in the distal ileal loops, and 3 cm colon loops) were taken out to prepare the electron microscopy section and observe the microscopic changes of the gastrointestinal mucosa. Results The mNSS in the TBI and Ghrelin groups was higher than that in the sham operation group after 24, 48 and 72 hours (P<0.01). The mNSS in the TBI group was higher than that in the Ghrelin group after 24, 48 and 72 hours (P<0.01). In the sham operation group, the intestinal wall was pink. In the TBI group, gastric dilatation and thinner wall with pale or dark red color were seen, and small intestine cavity expansion with dark color and even congestion were observed. There was much mucus in the intestinal wall. The Ghrelin group improved obviously than the TBI group after 6 hours. Compared with the Ghrelin group, the percentage of fecal water content in the TBI group decreased significantly after 24 hours (P<0.05), and the decrease rate dropped with time. Obvious delayed gastric emptying occurred (P<0.05), and the percentage of gastric contents in body weight demonstrated downtrend. The changes of gastric mucosa were as follows: the chief cells in the gastric glands were observed 72 hours after TBI in the TBI group, and scattered short microvilli were seen in the cell surface. The cytoplasm protruded into the glandular cavity, and a large number of rough endoplasmic reticulum could be seen in the cytoplasm, with irregular arrangement. Medullary bodies could be seen inside the mitochondria which swelled locally. Abundant endocrine granules were seen in the cytoplasm. Mitochondria were scattered and swollen, and mitochondria cristae became shorter and fewer, which contained medullary bodies. The Ghrelin group improved obviously than TBI group after 72 hours in terms of gastric mucosa changes. With respect to cecum mucosa, in the TBI group 72 hours after TBI, severe edema of the cecum absorption epithelium, obvious dilation of the rough endoplasmic reticulum, expansion of the free water gap inside the cell, and local decrease of the microvilli at the top of the cell were observed. Abundant microvilli were seen in the cecum absorption epithelium and cell top. The connection complex composed of tight connections, intermediate connections, and bridging particle connections could be seen between cells. The Ghrelin group improved obviously than TBI group after 72 hours in terms of cecum mucosa changes. Conclusions Ghrelin can improve gastrointestinal motility and protect gastrointestinal mucosa in rats after TBI. Key words: Brain injuries; Gastrointestinal motility; Ghrelin

Objective To explore the role of TLR4/NF-kB signal pathway in rat nerve injury after traumatic brain injury coupled with seawater drowning. Methods A total of 96 male Sprague-Dawley rats were randomly divided into 3 groups: the sham surgery group(n=12), the traumatic brain injury (TBI) group(n=42)and the traumatic brain injury coupled with seawater drowning group (or the TBI + SWD group)(n=42). At the timepoints of 3, 6, 12, 24, 72 and 168 hours after the establishment of the TBI model, immunohistochemistry was used to detect the expression of TLR4 and NF-kB cells in the rat brain tissue. Real time PCR (rt-PCR) was applied to detect the expression levels of TLR4 and NF-kB mRNA in the hippocampus of the brain tissue, and enzyme-linked immunosorbent assay(ELISA)was employed to detect the content of TNF-α in the rat brain tissue. Results The number of TLR4 and NF-kB positive cells in the brain tissue of the TBI group and the TBI + searwater drowning group increased. The expressions of TLR4 and NF-kB mRNA in the hippocampus of the brain tissue of the TBI group and the TBI + SWD group significantly increased 3 hours after establishment of the TBI model. For the TBI group, the expressions of TLR4 and NF-kB were respectively (1.63±0.52) and (1.52±0.41), while in the the TBI + SWD group, the expressions of the above 2 substantce were respectively (4 1.87±0.93) and (1.87±0.93). At hour 24, the expression reached peak. For the TBI group, the expressions of TLR4 and NF-kB were respectively (49.61±0.34) and (4.60±0.51), while for the the TBI + SWD group, the expressions of the above 2 substantces were respectively (16.11±0.49) and (5.80±0.52), then they decreased gradually. The expression levels of TNF-α in the TBI group and the TBI + SWD group were found to elevate 3 hours after establishment of the model. TNF-α expression level for the TBI group was (53.68±1.48) ng/L), while the expression level of the same substance for the TBI + SWD group was (60.14±2.06) ng/L. Wave peak appeared at hour 12, and the wave peak for the TBI group was (79.28±2.46) ng/L, while for the TBI + SWD group, it displayed at (103.51±5.53) ng/L. Conclusion Seawater drowning could aggravate nerve inflammatory response mediated by TLR4/NF-kB signal pathway, which might play an important role in the rat brain injury induced by trauma. Key words: Traumatic brain injury; Seawater drowning; TLR4; NF-kB; TNF-α

Cognitive and structural brain abnormalities are common following traumatic brain injury (TBI). The authors compared cognition and brain structure in 14 TBI survivors and 28 matched healthy comparison subjects. TBI survivors showed reduced cerebral volume, due mainly to white matter changes, and poorer attention, psychomotor speed, and memory. Severity of white matter abnormality correlated with worse performance on several cognitive measures that distinguished between groups. Using voxel-based morphometry, regions of reduced white matter concentration were found throughout the cerebrum along with more localized gray matter reductions. Findings suggest that diffuse rather than focal aspects of TBI contribute most to cognitive outcome.

Does donor cause of death affect the outcome of lung transplantation?

Objective To construct and evaluate a mouse model of traumatic brain injury (TBI) that simulates both motor and cognitive impairment. Methods Twenty-four healthy male C57BL/6 mice were randomly divided into a sham group and a TBI group (n=12/group). The TBI model was prepared by referring to the compression injury model with some modifications. The sham group underwent an identical process without mechanical trauma. Motor function was evaluated using the rotarod and beam-walking tasks at 1, 3, 7, 14, 21, 28 days post-injury. Spatial learning and memory capacities were assessed at 28, 29, 30, 31, 32, 33 days post-injury by the Morris Water Maze (MWM) test. Nissl staining was performed to observe pathological changes and immunofluorescence staining to detect the expression of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor protein (Iba-1) in the mouse brain on the 34th day after modeling. Results The latency for the TBI group was significantly lower than that for the sham group, and the frequency of slipping off the beam by the right hindlimbs for the TBI group was significantly higher than that for the sham group at 1, 3, 7, 14, 21, 28 days post-injury (P<0.05). The escape latency for the TBI group was significantly longer than that for the sham group in the MWM test at 30, 31 and 32 days after modeling (P<0.05). The times of crossing the platform for the TBI group were significantly less than those for the sham group at day 33 after TBI (P< 0.05). The lesion volume for the sham group was significantly smaller than that for the TBI group [(0.55±0.06)% vs. (16.90±1.14)%, P<0.05]. The numbers of astrocytes in the TBI and sham groups were respectively 101.40±6.18/mm2 and 20.17±1.55/mm2, and the numbers of microglia in the 2 groups were respectively 119.20±6.28/mm2 and 23.58±1.72/mm2, showing statistically significant differences between the 2 groups (P<0.05). Conclusion Since the TBI model we constructed is simple and reproducible with stable motor deficits and cognitive impairments which are consistent with the pathological changes of moderate TBI, it can be used in animal TRI experiments. Key words: Traumatic brain injury; Model, animal; Movement deficit; Cognitive impairment

Pediatric Head Injury

Objective To investigate the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation on brain edema, autophagy response and neurobehavioral outcome after traumatic brain injury (TBI) in rats and the related mechanisms. Methods TBI rat models were established using Feeney's method. Seventy-two SD rats were divided into 4 groups using random number table: sham operation group, TBI group, ω-3 PUFA supplementation group (TBI+ ω-3 group) and autophagy inhibitor 3-methyladenine group (TBI+ 3-MA group) (all n=18), each group was further divided into 3 sub-groups (n=6) corresponding to 3 time points (days 1, 3, and 7 after TBI). On each of the 3 time points, we measured rat behavioral outcomes with modified neurologic severity score (mNSS) tests; brain water content was measured with wet-dry weight method. The mRNA and protein expressions of autophagy-related factors (LC3-Ⅱ and Beclin-1) in TBI cerebral cortex were determined by immunohistochemistry staining, reverse transcription-polymerase chain reaction and Western blot on day 3 after TBI. Results Compared with the sham group, on days 1, 3, and 7 after injuary, the TBI group, the TBI+ ω-3 group, and the TBI+ 3-MA group had significantly higher mNSS scores (TBI group: 12.42±0.27 vs.1.34±0.32, 12.07±0.27 vs. 1.16±0.29, 10.22±0.39 vs. 1.22±0.30; TBI+ ω-3 group: 12.05±0.23 vs. 1.34±0.32, 11.38±0.21 vs. 1.16±0.29, 8.20±0.21 vs. 1.22±0.30; TBI+ 3-MA group: 11.93±0.20 vs. 1.34±0.32, 11.09±0.19 vs. 1.16±0.29, 7.93±0.17 vs. 1.22±0.30; all P=0.00) and brain water content [TBI group: (79.82±0.61)% vs. (71.87±0.43)%, (83.04±0.42)% vs. (72.13±0.53)%, (75.12±0.72)% vs. (71.78±0.38)%; TBI+ ω-3 group: (76.81±0.63)% vs. (71.87±0.43)%, (79.39±0.59)% vs. (72.13±0.53)%, (73.86±0.38)% vs. (71.78±0.38)%; TBI+ 3-MA group: (75.98±0.49)% vs. (71.87±0.43)%, (77.14±0.46)% vs. (72.13±0.53)%, (72.24±0.37)% vs. (71.78±0.38)%; all P=0.00]. The mRNA and protein expressions of LC3-Ⅱ and Beclin-1 in the brain were also significantly higher on day 3 in the TBI group, the TBI+ ω-3 group, and the TBI+ 3-MA group (all P=0.00). Compared with the TBl group, on day 3 and day 7 after injury, the TBI+ ω-3 group and the TBI+ 3-MA group had significantly lower mNSS scores (TBI+ ω-3 group: 11.38±0.21 vs. 12.07±0.27, P=0.04, 8.20±0.21 vs. 10.22±0.39, P=0.01; TBI+ 3-MA group: 11.09±0.19 vs. 12.07±0.27, P=0.01, 7.93±0.17 vs. 10.22±0.39, P=0.00). On days 1, 3, and 7, compared with the TBI group, the TBI+ ω-3 group and the TBI+ 3-MA group had significantly lower brain water content [TBI+ ω-3 group: (76.81±0.63)% vs. (79.82±0.61)%, P=0.04, (79.39±0.59)% vs. (83.04±0.42)%, P=0.01, (73.86±0.38)% vs. (75.12±0.72)%, P=0.03; TBI+ 3-MA group: (75.98±0.49)% vs. (79.82±0.61)%, P=0.01, (77.14±0.46)% vs. (83.04±0.42)%, P=0.00, (72.24±0.37)% vs. (75.12±0.72)%, P=0.02]. On day 3, the TBI+ ω-3 group and the TBI+ 3-MA group had significantly reduced LC3-Ⅱ and Beclin-1 mRNA expression compared with the TBI group (TBI+ ω-3 group: P=0.04, P=0.01; TBI+ 3-MA group: P=0.01, P=0.00) and protein expression (TBI+ ω-3 group: P=0.01, P=0.03; TBI+ 3-MA group: both P=0.00). Conclusion ω-3 PUFA supplementation could markedly reduce brain edema and improve neurological functions after TBI, showing a neuroprotective effect, possibly through inhibiting TBI-induced autophagy responses. Key words: Traumatic brain injury; Omega-3 polyunsaturated fatty acids; Autophagy; Neuroprotection

Venous thrombus embolism (VTE) is common after polytrauma, both of which are considered significant contributors to poor outcomes and mortality. Traumatic brain injury (TBI) is recognized as an independent risk factor for VTE and one of the most common components of polytraumatic injuries. Few studies have assessed the impact of TBI on the development of VTE in polytrauma patients. This study sought to determine whether TBI further increases the risk for VTE in polytrauma patients. A retrospective, multi-center trial was performed from May 2020 to December 2021. The occurrence of venous thrombosis and pulmonary embolism from injury to 28 days after injury was observed. Of 847 enrolled patients, 220 (26%) developed DVT. The incidence of DVT was 31.9% (122/383) in patients with polytrauma with TBI (PT + TBI group), 22.0% (54/246) in patients with polytrauma without TBI (PT group), and 20.2% (44/218) in patients with isolated TBI (TBI group). Despite similar Glasgow Coma Scale scores, the incidence of DVT in the PT + TBI group was significantly higher than in the TBI group (31.9% vs. 20.2%, p < 0.01). Similarly, despite no difference in Injury Severity Scores between the PT + TBI and PT groups, the DVT rate was significantly higher in the PT + TBI group than in the PT group (31.9% vs. 22.0%, p < 0.01). Delayed anticoagulant therapy, delayed mechanical prophylaxis, older age, and higher D-dimer levels were independent predictive risk factors for DVT occurrence in the PT + TBI group. The incidence of PE within the whole population was 6.9% (59/847). Most patients with PE were in the PT + TBI group (64.4%, 38/59), and the PE rate was significantly higher in the PT + TBI group compared to the PT (p < 0.01) or TBI (p < 0.05) group. In conclusion, this study characterizes polytrauma patients at high risk for VTE occurrence and emphasizes that TBI markedly increases the incidence of DVT and PE in polytrauma patients. Delayed anticoagulant therapy and delayed mechanical prophylaxis were identified as the major risk factors for a higher incidence of VTE in polytrauma patients with TBI.

Background: In patients who have sustained a traumatic brain injury with an associated extremity fracture there is often a clinical perception that the rate of new bone formation around the fracture site is increased. In this study, we made a rat model of femoral fracture to investigate the serum factors changes in vivo. We examined the effects serum factors on fracture healing and the molecular signaling pathways that might link these two. Methods and Findings: Thirty-Six female Sprague-Dawley rats were randomly allocated into 4 groups; the non-operated control group, traumatic brain injury (TBI) group, bone fracture (Fr) group and the bone fracture/ TBI group (TBI & Fr) (n=9 per group). These animals were sacrificed at 6 weeks after experiments. Volume of callus in fracture was measured weekly with the Perkins volume formula at 2nd week after operation. The radiology imaging was interpreted by two or more senior orthopedic specialists. In vivo chemo taxis assay by serum samples collected at the 1, 3, 7 and 14 days, and 3rd, 4th, 6th week after surgery. Seral NGF, Wnt, RANKL, Dkk-1, ACTH, Leptin titer was measured and analyzed. After 2 weeks operation, the formation of callus was found at the fracture site, callus in TBI & Fr group was slightly higher than Fr group; however, there was no significant difference existed between the TBI & Fr and Fr groups. The ACTH level was significantly elevated in the TBI & Fr group than other groups and attained its peak at 1 week after operation, while the leptin was shown higher levels in Fr groups than TBI and TBI & Fr groups at 2 weeks after operation. The serum insulin level was markedly increased in all experimental groups during 1-3 days after surgery; at the meanwhile, the serum glucose level only significantly increased in the Fx and TBI groups at the 1 and 3 day after operation. The serum of NGF levels in the groups with TBI process (TBI and TBI & Fr groups) was significantly higher than those of the simple fracture group and control group. In the early stage of bone fracture, DKK-1 should be more active than Wnt-3a and NGF; later Wnt-3a and NGF became active to stimulate the osteoblasts for bone formation. After 3 day to 2 week of surgery, the RANKL process was drove to additional bone remodeling in accompany with bone formation. Conclusions: Through this project, the pathogenesis of increased rates of excessive bone healing in the patients with traumatic brain injury will be elucidated for the future study on clinical treatment in both traumatic brain injury and fracture healing. Keywords: Traumatic brain injury, fracture healing,

OBJECTIVES/SPECIFIC AIMS: Analyze data from the first 30 children enrolled in a prospective cohort study evaluating the ability of specific serum biomarkers to distinguish children with traumatic brain injuries (TBI) from children with orthopedic injuries (OI). METHODS/STUDY POPULATION: Children ages 0&lt;5 years were eligible if they presented to the emergency department within 6 hours of injury. Children were identified as having a TBI if they sustained a head injury and were found to have an acute injury on head CT. Children were identified as having an OI if they sustained a musculoskeletal injury significant enough to necessitate radiography per clinical care. Individual (eg, age) and clinical (eg, radiography findings) factors, as well as serum biomarkers [eg, ubiquitin C-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP)] were collected at time of enrollment. TBI and OI groups were compared using Wilcoxon rank-sum and Kruskal-Wallis tests. RESULTS/ANTICIPATED RESULTS: This cohort consisted of 13 children with TBI (7 with isolated skull fractures, 1 with intracranial injury, and 5 with both a skull fracture and an intracranial injury) and 17 with OI (12 with fractures). Most patients were male (67%) and White (67%), and this did not differ between groups (p&gt;0.1). Children with TBI were significantly younger than children with OI, with an average (±standard deviation) age of 15±13 and 39±13 months, respectively (p&lt;0.01). There was not a significant difference in time from injury to biomarker collection between TBI and OI patients at 4.1±1.8 and 5.8±2.6 hours, respectively (p=0.07). Median (IQR) levels of GFAP were significantly higher (p&lt;0.01) in children with TBI, relative to children with OI: 220 (67–421) pg/mL Versus 37 (25–74) pg/mL, respectively. Median (IQR) levels of UCH-L1 were also significantly higher (p&lt;0.01) in the TBI group, relative to children with OI: 444 (377–449) pg/mL Versus 248 (140–417) pg/mL, respectively. In a subanalysis comparing median biomarker levels across three study groups (ie, TBI with an isolated skull fracture, TBI with an intracranial injury, and OI), group differences remained significant for both biomarkers with TBI patients having higher levels, relative to OI patients, of both GFAP (p&lt;0.01) and UCH-L1 (p=0.02). DISCUSSION/SIGNIFICANCE OF IMPACT: GFAP and UCH-L1 hold promise to improve the diagnosis of TBI in very young children. Identification of a marker of TBI that can be done in the acute care setting would advance the diagnosis of TBI in very young children, a vulnerable population for whom identification of neurological symptoms can be challenging.

Wakefulness-Promoting Effects of Lateral Hypothalamic Area–Deep Brain Stimulation in Traumatic Brain Injury-Induced Comatose Rats: Upregulation of α1-Adrenoceptor Subtypes and Downregulation of Gamma-Aminobutyric Acid β Receptor Expression Via the Orexins Pathway

Purpose: To study the influence of naloxone hydrochloride on traumatic brain injury (TBI).&#x0D; Methods: Three groups of rats were used: normal control, TBI, and TBI + naloxone hydrochloride groups (12 rats/group). In the control group, only the osseous foramen was opened. Rats in TBI group were intraperitoneally injected with normal saline, while the naloxone group received naloxone hydrochloride injection at the same time. Changes in peripheral blood β-EP, CD4+, CD8+, IL-2, and S100-B levels; and brain tissue MMP-9 were assessed.&#x0D; Results: The levels of β-EP in the TBI- and naloxone-treated rats were higher than control values, while levels of CD4+ in TBI and naloxone groups were significantly lower than those of control group (p &lt; 0.01). At every time point, CD8+ level in naloxone group was significantly lower than that in TBI group (p &lt; 0.01). Compared with control group, the levels of IL-2 in the TBI and naloxone groups were significantly lower. Higher levels of S100-B were seen in TBI- and naloxone-treated rats, relative to control value. In the naloxone group, MMP-9 expression was downregulated, when compared to the expression TBI rats (p &lt; 0.05).&#x0D; Conclusion: Naloxone hydrochloride reduces β-EP, alleviates inflammation, protects nerve cells and reduces brain injury in TBI rats. There is, thus, a potential to develop naloxone for the management of brain injury

Objective To investigate the apoptosis expression and role of calcium sensing receptor (CaSR) induced by traumatic brain injury (TBI) in rats. Methods Fifty-four healthy male SD rats were randomly divided into 3 groups: the control group, TBI group and inhibitor group (n=18). Each group was divided into 3 subgroups: 6 hours, 24 hours, and 72 hours (n=6). TBI animal models in the TBI and inhibitor groups were established using Feeney＇s method. CaSR antagonist NPS2390 (10 μmol/kg) was infused through caudal vein for 2 days before the establishment in the inhibitor group. Modified Neurological Severity Scores (mNSS) was used to evaluate the neurological behavior of rats in each group. Real-Time PCR was used to detect expressions of CaSR and Caspase-3 mRNA. Western blot was used to detect the protein expression of CaSR and Caspase-3 protein. TUNEL assay was used to detect neuronal apoptosis. Results (1) The results showed that the mNSS scores in TBI group compared with the control group and inhibitor group were increased in 6 h, 24 h, 72 h after modeling (P<0.01). (2) In both TBI and inhibitor groups, the mRNA and protein expressions of CaSR and Caspase-3 reached the peak at 24h (P<0.01). Compared with the control group and the inhibitor group, the expression of CaSR mRNA and its protein were increased in the TBI group (P<0.01). The expression of Caspase-3 was higher in the TBI group than that in the control and inhibitor groups at 24 h only (P<0.05). (3) The results of TUNEL assay showed that apoptosis reached the peak level at 24 h after TBI model was made (P<0.05). The TBI group had more apoptotic cells compared with the other 2 groups (P<0.01). (4) There was a positive correlation between CaSR as well as Caspase-3 and neuronal apoptosis (r=0.300, P<0.05; r=0.371, P<0.01). The protein expressions of CaSR and Caspase-3 had a positive correlation (r=0.434, P<0.01). Conclusion CaSR may play an important role in neuronal apoptosis in the rat model of TBI. Key words: Craniocerebral trauma; Receptors, calcium-sensing; Apoptosis; Rats