# paper.pdf ## Metadata - PDFFormatVersion=1.4 - IsLinearized=false - IsAcroFormPresent=false - IsXFAPresent=false - IsCollectionPresent=false - IsSignaturesPresent=false - CreationDate=D:20260511184422Z - ModDate=D:20260514110617-07'00' - Producer=macOS Version 26.4.1 (Build 25E253) Quartz PDFContext - xmp:createdate=2026-05-11T18:44:22Z - xmp:modifydate=2026-05-14T11:06:17-07:00 - xmp:metadatadate=2026-05-14T11:06:17-07:00 - pdf:producer=macOS Version 26.4.1 (Build 25E253) Quartz PDFContext - dc:format=application/pdf - xmpmm:documentid=uuid:f32e8ef7-ec69-4c43-8bef-719e8e348e39 - xmpmm:instanceid=uuid:b350ced1-81e7-1249-8355-36ff20ea79b6 ## Contents ### Page 1 Neuronal Toll-like Receptor-4 regulation of Matrix Metalloproteinase-9 ActivityMediates Dentate Circuit Dysfunction after Traumatic Brain InjuryDeepak Subramanian1#, Erick Contreras1, Laura Dovek2, Razieh Jaberi1, Emmanuel Green1,Ysabelle K Lao1, Iryna M Ethell2 and Vijayalakshmi Santhakumar1# ### Page 2 Supplementary Figure 1: Absence of overt histopathological changes and consistent dentate gyrus hilar cell loss a;er Lateral Fluid Percussion Injury. A) Representa7ve images of Nissl- stained slices from 3 sham and 3 FPI rats 1-month post-injury showing no gross structural damage. B) Representa7ve Nissl-stained images showing reduced hilar neurons in injured animals. C) Summary plot shows injury-induced decrease in hilar neuron count. n = 4 sham and 3 FPI rats. ** indicates P<0.01 by unpaired t-test. ### Page 3 Supplementary Figure 2: TLR4 signaling drives changes in miniature excitatory and inhibitoryinputs to DGCs a=er brain injury. A) Representa7ve granule cell mEPSC traces from vehicletreated sham controls (black), vehicle treated FPI (red), TLR4 inhibited sham (grey) and TLR4inhibited FPI (blue) rats. B-C) Cumula7ve probability plots of mEPSC interevent intervals (B) andamplitude (C) in experimental groups. D) Representa7ve mIPSC traces from granule cells invehicle treated sham controls (black), vehicle treated FPI (red), TLR4 inhibited sham (grey) andTLR4 inhibited FPI (blue) rats. E-F) Cumula7ve probability plots of mIPSC interevent intervals (E)and amplitude(F) in vehicle treated and TLR4 inhibited sham and injured rats. n = 7 cells from 3rats/group *indicates P<0.05 by Holm-Bonferroni corrected K.S. test.SHAMDMSOFPIDMSOSHAMTAK-2420 10 20 30 400.00.20.40.60.81.0Amplitude (pA)Cumulative ProbabilityFPITAK-242A DCB 20 pA0.2 s20 pA0.5 sMiniature EPSC Miniature IPSCSHAMDMSO vs FPIDMSOFPIDMSO vs FPITAK-242SHAMDMSO vs SHAMTAK-242SHAMDMSO vs FPIDMSOFPIDMSO vs FPITAK-242SHAMDMSO vs SHAMTAK-242 SHAMDMSO vs FPIDMSO nsSHAMDMSO vs FPIDMSOFPIDMSO vs FPITAK-242SHAMDMSO vs SHAMTAK-242 nsFE********0 2000 4000 60000.00.20.40.60.81.0Interevent Interval (msec)Cumulative Probability0 500 1000 1500 20000.00.20.40.60.81.0Interevent Interval (msec)Cumulative probability0 10 20 30 40 50 600.00.20.40.60.81.0Amplitude (pA)Cumulative probabilitymEPSC IEI mEPSC amplitude mIPSC IEI mIPSC amplitude ### Page 4 Supplementary Figure 3: ValidaAon of cell-type specific TLR4 deleAon in DG glutamatergicneurons. A) Experimental 7meline for evalua7ng TLR4 expression a[er tamoxifen induc7on inTLR4fl/fl: CaMKIIa-CreERT2 mice and li_ermate Cre-ve mice. B) Representa7ve images of TLR4expression in the DG of tamoxifen treated to Cre-ve and TLR4fl/fl: CaMKIIa-CreERT2 mice 3 daysa[er injury. C) Summary plot of TLR4 expression in experimental groups. * indicates P<0.05 bynested t-test based on n = 5-6 slices / mouse (indicated as animal number on x-axis) from 3mice/group. D) Experimental 7meline for evalua7ng TLR4 mRNA a[er tamoxifen induc7on inTLR4fl/fl: CaMKIIa-CreERT2 mice and li_ermate Cre-ve mice. E) Representa7ve images of TLR4mRNA expression in the DG of a wild-type sham mouse, tamoxifen treated to Cre-ve and TLR4fl/fl:CaMKIIa-CreERT2 mice 3 days a[er injury and a nega7ve control. F) Summary plot of TLR4 mRNA ### Page 5 expression in the granule cell layer (GCL) in experimental groups. * indicates P<0.05 and **indicates P<0.01 by OW-ANOVA, based on data averaged across sec7ons from n = 3-5 mice/group. ### Page 6 Supplementary Figure 4: Effects of selecAve TLR4 deleAon in glutamatergic neurons on DGCproperAes. A) Experimental 7meline for examining ac7ve and passive proper7es of DGCs fromTLR4fl/fl: CaMKIIa-CreERT2 mice. B-F) Summary plots of ac7ve and passive proper7es includingcapacitance (B), res7ng membrane poten7al (C), input resistance (D), Rheobase (E) and spikefrequency (F) in Cre-ve and Cre+ve sham and FPI mice. Note the effect of genotype on cellcapacitance and firing frequency in sham injured mice. Also note that the res7ng membranepoten7al is significantly depolarized Cre+ve mice a[er injury, but no differences are seen in Cre-vemice. Data points in panels B-E represent individual cells (n = 7 cells from 3 mice/group). G) ### Page 7 Experimental 7meline for in situ zymography experiments. H) Representa7ve images from slicesincubated in MMP-9 blocker SB-3CT that served as nega7ve controls. I-J) Quan7fica7on of DQ-fluorescence showing CA1 Str. Radiatum intensity is unaltered by injury, treatments or genotype.* indicates P<0.05 by TW-ANOVA with Šídáks mul7ple comparisons post hoc tests (B-F) and OW-ANOVA (I-J). Data points in panel I and J represent individual animals (n = 5-6 rats/group, and 3-4mice / group, respec7vely). ### Page 8 Supplementary Figure 5: MMP-9 inhibiAon modulates mEPSC amplitude without rescuingchanges in sIPSC frequency or amplitude. A) Experimental 7meline for examining changes insynap7c inputs to DGCs in acute rat slices a[er LPS incuba7on. B-C) Cumula7ve probability plotsof granule cell sIPSC (B) and mIPSC (C) interevent intervals in sham, LPS-B5 incubated (orange)and LPS-B5+SB-3CT (magenta) co-incubated slices. Note that while LPS-B5 incuba7on did notalter sIPSC, mIPSC interevent intervals were significantly reduced. Co-incuba7on of slices inMMP-9 blocker SB-3CT prevented this change. D) Representa7ve granule cell mEPSC traces fromSB-3CT treated sham (grey) and injured rats (green). E-F) Cumula7ve probability plots of mEPSCinterevent intervals (E) and amplitude (F) in SB-3CT treated sham/injured rats. G)Representa7ve granule cell sIPSC recordings from SB-3CT treated sham (grey) and injured rats(green). H-I) Cumula7ve probability plots of mEPSC interevent intervals (H) and amplitude (I)between SB-3CT treated sham/injured rats. n = 8 cells from 4 rats/group (A-C), 7-9 cells from 3rats/group (D-F) and 8-13 cells from 3 rats/group (G-I) *indicates P<0.05 by Holm-Bonferronicorrected K.S. test.0 200 400 600 800 15000.00.20.40.60.81.0Interevent Interval (msec)Cumulative probability0 10 20 30 40 50 600.00.20.40.60.81.0Amplitude (pA)Cumulative probability0 200 400 600 800 15000.00.20.40.60.81.0Interevent Interval (msec)Cumulative probability0 10 20 30 400.00.20.40.60.81.0Amplitude (pA)Cumulative ProbabilityMiniature EPSC20 pA0.2 sSHAMDMSO vs SHAMSB-3CTFPIDMSO vs FPISB-3CTSHAMDMSO vs SHAMSB-3CTFPIDMSO vs FPISB-3CT*ns *HSHAMDMSO vs SHAMSB-3CT50 pA0.5 sSpontaneous IPSCFPIDMSO vs FPISB-3CTSHAMDMSO vs SHAMSB-3CTFPIDMSO vs FPISB-3CT*nsGInsnsDE FSHAM vs SHAMLPS SHAMLPS vs SHAMLPS+SB-3CTnsSHAM vs SHAMLPS * *AB CMMP-9 INHIBITION*ShamP24 7 DPISlice incubationaCSF (or) LPS-B5 (or)LPS-B5 + SB-3CTPatch-Clamprecordings+ 90 min0 2000 4000 60000.00.20.40.60.81.0Interevent Interval (msec)Cumulative Probability0 500 1000 1500 20000.00.20.40.60.81.0Interevent Interval (msec)Cumulative probabilitymEPSC IEI mEPSC amplitude sIPSC IEI sIPSC amplitudemIPSC IEIsIPSC IEI ### Page 9 Supplementary Figure 6: Treatment with Tak-242 or SB-3CT miAgates SpaAal learning deficitsin brain injured rats. A) Representa7ve heat plots showing trajectory of drug-treated rats in theBarnes maze during task on day 2. B-C) Summary plot of latency to escape (B) and distancetravelled (C) on Barnes maze spa7al naviga7on task on day 4 or day 7 in untreated sham andinjured rats. D) Summary plot of speed of movement across the training days between thevehicle and drug-treated sham and injured animals showed no injury or training day differences.n = 6-10 rats/group. Data points in panel D represent individual animals.Day 1 Day 2 Day 30.000.050.100.150.200.25Movement speed (m/s)B CD SPEED!"#$% !"#$&D(D)DD)(D!"#&$*+",-./#012-$34-/5.64T !"#$%&'!"#$% !"#$&D()D)(!"#&*!+,-"./0!+,-"./0$123!"#$% !"#$&D(D)DD)(D!"#&*+",-.L#012-$34-L5.64T!"#$% !"#$&D()D)(!"#&*!+,-"./0!+,-"./0$123Day 4 Day 7 Day 4 Day 7LATENCY DISTANCEAShamDMSOShamTAK-242ShamSB-3CTFPIDMSOFPITAK-242FPISB-3CTShamTAK-242 FPITAK-242ShamSB-3CT FPISB-3CTtime spent time spenttime spenttime spent ### Page 10 TABLE 1:Spontaneous EPSCInterevent intervals AmplitudeMean(ms) Median InterquartilerangeMean(pA) Median Interquartilerangen(cells)SHAMDMSO 336.9 216.4 86.05 - 429.9 13.16 12.20 9.99-15.36 8FPIDMSO 225.3 144.8 64.60 - 307.4 11.23 10.31 8.06-13.42 8SHAMTAK-242 221.8 143.6 65.74 - 285.6 13.20 12.23 9.64-15.77 9FPITAK-242 321.9 204.2 95.08 - 420.2 13.82 12.49 9.80-16.20 8SHAMLPS-B5 265.3 157.3 69.18 - 330.4 17.86 17.29 14.06-21.09 8SHAMLPS-B5+SB-3CT 339.7 230.9 94.53 - 434.6 15.90 14.66 11.53-18.96 9SHAMSB-3CT 311.3 203.5 81.18 - 396.8 12.45 11.38 9.22-14.57 10FPISB-3CT 495.6 303.8 119.8 - 632.3 12.60 11.64 9.29-14.88 9Spontaneous IPSCSHAMDMSO 190.3 128.1 65.35 - 242.4 16.66 13.78 10.81-19.21 8FPIDMSO 256.6 181.1 83.78 - 320.4 18.24 15.74 11.94-21.70 8SHAMTAK-242 174.2 102.4 50.75 - 199.2 14.79 12.98 10.27-16.85 8FPITAK-242 200.9 119.7 61.08 - 252 19.95 14.18 10.58-23.23 7SHAMLPS-B5 197.8 128.6 63.33 - 247.5 15.56 13.52 10.99-17.58 8SHAMLPS-B5+SB-3CT 294.3 206.4 92.83 - 395.6 18.01 16.17 12.30-21.37 10SHAMSB-3CT 208.3 135.9 69.60 - 255.9 16.96 14.77 11.16-20.12 13FPISB-3CT 288.3 177.2 73.75 - 361.9 18.71 16.28 12.78-21.90 8TLR4fl/fl-CaMKIIa-CreERT2 mice – Spontaneous EPSCMean(sec) Median InterquartilerangeMean(pA) Median Interquartilerangen(cells)Cre-ve SHAM 2.154 1.291 0.45-2.74 13.42 11.65 10.03-14 7Cre-ve FPI 1.234 0.721 0.31-1.79 11.29 10.36 8.62-12.73 7Cre-ve FPISB-3CT 1.734 0.997 0.36-2.24 10.05 9.222 7.57-11.43 7Cre+ve SHAM 2.223 1.271 0.49-3.10 12.01 11.19 8.90-13.62 6Cre+ve FPI 1.904 1.203 0.41-2.46 11.27 10.42 8.46-12.65 7 ### Page 11 Table 1. Descriptive statistics dentate gyrus cells (DGCs) physiology followingtraumatic brain injury. Summary of descriptive statistics of interevent intervals andamplitude of spontaneous excitatory and inhibitory postsynaptic currents recorded fromDGCs. n represents cells recorded from 3-4 animals/group. ### Page 12 TABLE 2:Miniature EPSCInterevent intervals AmplitudeMean(ms) Median InterquartilerangeMean(pA) Median Interquartilerangen(cells)SHAMDMSO 824.8 496.1 208.1 - 1096 14.16 12.32 8.90-17.91 7FPIDMSO 642.4 396.4 158.2 - 858.6 9.28 8.02 6.55-10.55 7SHAMTAK-242 615.2 325.4 130 - 749.2 12.24 10.54 8.15-15.13 8FPITAK-242 1648 621.2 234.5 - 1959 13.82 12.49 9.80-16.20 8SHAMLPS-B5 726.5 467.7 189.6 - 982.4 10.04 9.219 7.37-11.74 6SHAMLPS-B5+SB-3CT 1014 551.1 197.5 - 1272 12.75 11.23 9.53-14.44 10SHAMSB-3CT 1313 624.1 243.6 - 1660 10.22 9.30 7.63-11.82 9FPISB-3CT 710.5 346.9 146.9 - 784.7 12.36 10.85 8.74-14.04 7Miniature IPSCInterevent intervals AmplitudeMean(ms) Median InterquartilerangeMean(pA) Median Interquartilerangen(cells)SHAMDMSO 254.7 161.2 77.05 - 318.9 15.72 14.15 10.99-18.58 7FPIDMSO 251 171 86.30 - 336.7 17.68 15.20 11.58-20.72 7SHAMTAK-242 217.6 150.1 74.63 - 286.1 15.14 13.72 10.54-18.27 7FPITAK-242 251 143 64.70 - 300.6 13.75 12.23 9.26-16.35 6SHAMLPS-B5 183.8 124.9 60.13 - 244.1 14.06 12.56 10.04-16.53 6SHAMLPS-B5+SB-3CT 321.6 216.9 90.60 - 420 18.05 16.33 13.19-21.49 10SHAMSB-3CT 218.1 140 63.63 - 287.2 15.95 14.31 11.41-18.37 11FPISB-3CT 366.4 208.1 93.60 - 462.2 16.67 14.90 11.47-19.80 7 ### Page 13 Table 2. Descriptive statistics dentate gyrus cells (DGCs) physiology followingtraumatic brain injury. Summary of descriptive statistics of interevent intervals andamplitude of miniature excitatory and inhibitory postsynaptic currents recorded from DGCs.n represents cells recorded from 3-4 animals/group. ### Page 14 TABLE 3: Holm-Šídák Adjusted P-valuesExcitatory currentsSpontaneous MiniatureIEI amplitude IEI amplitudeSHAMDMSO (vs) FPIDMSO P<0.0001;d = 0.344P<0.0001;d = 0.410P=0.0027;d =0.217P<0.0001;d = 0.853FPIDMSO (vs) FPITAK-242 P<0.0001;d = 0.615P<0.0001;d =0.502P<0.0001;d =0.543P<0.0001;d = 0.889SHAMDMSO (vs) SHAMTAK-242P<0.0001;d = 0.354P=0.5297;d = 0.008P<0.0001;d =0.239P<0.0001;d = 0.301SHAMDMSO (vs) ShamLPS P<0.0001;d = 0.202P<0.0001;d = 0.766P=0.2463;d = 0.113P<0.0001;d = 0.788ShamLPS (vs) ShamLPS + SB-3CT P<0.0001;d = 0.216P<0.0001;d = 0.325P=0.0012;d = 0.237P<0.0001;d = 0.538SHAMDMSO (vs) ShamSB-3CT P =0.6476;d = 0.069P =0.0002;d = 0.147P =0.0001;d = 0.311P<0.0001;d = 0.738FPIDMSO (vs) FPISB-3CTP<0.0001;d = 0.601P<0.0001;d = 0.301P =0.1108;d = 0.073P<0.0001;d = 0.620Inhibitory currentsSHAMDMSO (vs) FPIDMSOP<0.0001;d = 0.290P<0.0001;d = 0.157P=0.5139;d = 0.013P=0.0044;d = 0.220FPIDMSO (vs) FPITAK-242P<0.0001;d = 0.221P<0.0001;d = 0.112P=0.0748;d =0.000P<0.0001;d = 0.473SHAMDMSO (vs) SHAMTAK-242 P=0.0005;d = 0.072P=0.0037;d = 0.206P=0.5139;d = 0.419P=0.3 808;d = 0.077SHAMDMSO (vs) ShamLPSP=0.8642;d = 0.037P=0.0222;d = 0.107P=0.0004;d = 0.293P<0.0001;d =0.226ShamLPS (vs) ShamLPS + SB-3CTP<0.0001;d =0.378P<0.0001;d = 0.246P<0.0001;d = 0.468P<0.0001;d = 0.549SHAMDMSO (vs) ShamSB-3CT P=0.4758;d = 0.085P<0.0001;d =0.138P=0.0542;d = 0.146P=0.2826;d =0.030FPIDMSO (vs) FPISB-3CTP=0.4287;d = 0.098P=0.0597;d = 0.048P=0.0012;d = 0.299P=0.5412;d = 0.113TLR4fl/fl-CaMKIIa-CreERT2 mice – Spontaneous Excitatory currentsCre-ve SHAM (vs) Cre-ve FPI P<0.0001;d = 0.420P<0.0001;d = 0.311Cre+ve SHAM (vs) Cre+ve FPI P=0.1109;d = 0.131P=0.0008;d = 0.157Cre-ve FPI vs Cre-ve FPISB-3CT P<0.0001;d = 0.283P<0.0001;d = 0.303Excitatory currentsSpontaneous MiniatureIEI amplitude IEI amplitudeSHAMDMSO (vs) FPIDMSO P<0.0001;d = 0.344P<0.0001;d = 0.410P=0.0027;d =0.217P<0.0001;d = 0.853FPIDMSO (vs) FPITAK-242 P<0.0001;d = 0.615P<0.0001;d =0.502P<0.0001;d =0.543P<0.0001;d = 0.889SHAMDMSO (vs) SHAMTAK-242P<0.0001;d = 0.354P=0.5297;d = 0.008P<0.0001;d =0.239P<0.0001;d = 0.301SHAMDMSO (vs) ShamLPS P<0.0001;d = 0.202P<0.0001;d = 0.766P=0.2463;d = 0.113P<0.0001;d = 0.788ShamLPS (vs) ShamLPS + SB-3CT P<0.0001;d = 0.216P<0.0001;d = 0.325P=0.0012;d = 0.237P<0.0001;d = 0.538SHAMDMSO (vs) ShamSB-3CT P =0.6476;d = 0.069P =0.0002;d = 0.147P =0.0001;d = 0.311P<0.0001;d = 0.738FPIDMSO (vs) FPISB-3CTP<0.0001;d = 0.601P<0.0001;d = 0.301P =0.1108;d = 0.073P<0.0001;d = 0.620Inhibitory currentsSHAMDMSO (vs) FPIDMSOP<0.0001;d = 0.290P<0.0001;d = 0.157P=0.5139;d = 0.013P=0.0044;d = 0.220FPIDMSO (vs) FPITAK-242P<0.0001;d = 0.221P<0.0001;d = 0.112P=0.0748;d =0.000P<0.0001;d = 0.473SHAMDMSO (vs) SHAMTAK-242 P=0.0005;d = 0.072P=0.0037;d = 0.206P=0.5139;d = 0.419P=0.3 808;d = 0.077SHAMDMSO (vs) ShamLPSP=0.8642;d = 0.037P=0.0222;d = 0.107P=0.0004;d = 0.293P<0.0001;d =0.226ShamLPS (vs) ShamLPS + SB-3CTP<0.0001;d =0.378P<0.0001;d = 0.246P<0.0001;d = 0.468P<0.0001;d = 0.549SHAMDMSO (vs) ShamSB-3CT P=0.4758;d = 0.085P<0.0001;d =0.138P=0.0542;d = 0.146P=0.2826;d =0.030FPIDMSO (vs) FPISB-3CTP=0.4287;d = 0.098P=0.0597;d = 0.048P=0.0012;d = 0.299P=0.5412;d = 0.113TLR4fl/fl-CaMKIIa-CreERT2 mice – Spontaneous Excitatory currentsCre-ve SHAM (vs) Cre-ve FPI P<0.0001;d = 0.420P<0.0001;d = 0.311Cre+ve SHAM (vs) Cre+ve FPI P=0.1109;d = 0.131P=0.0008;d = 0.157Cre-ve FPI vs Cre-ve FPISB-3CT P<0.0001;d = 0.283P<0.0001;d = 0.303 ### Page 15 Table 3. Statistical analysis of synaptic inputs to dentate gyrus cells (DGCs) followingtraumatic brain injury. Summary of Holm-Bonferroni corrected P-values (Kolmogorov-Smirnov tests) and Cohen’s d eVect sizes for comparisons of synaptic inputs to DGCsbetween sham and FPI groups. Animals received either vehicle or the TLR4 inhibitor TAK-242.Parameters include interevent intervals and amplitudes for both spontaneous and miniatureexcitatory postsynaptic currents (sEPSC/mEPSC) and inhibitory postsynaptic currents(sIPSC/mIPSC). ### Page 16 TABLE4:10min 60min 120min 180minSHAMDMSO 157.71±6.58 144.00±4.30 146.78±4.82 145.15±7.03FPIDMSO 130.23±6.92 116.69±3.84 112.84±4.20 110.36±5.31SHAMTAK-242 150.12±7.95 133.00±5.58 124.33±8.60 116.11±6.98FPITAK-242 149.14±8.95 143.91±4.66 140.32±4.02 141.21±5.00SHAMSB-3CT 164.56±5.67 159.66±2.40 156.98±8.57 154.61±7.70FPISB-3CT 166.98±10.3 157.60±10 146.85±6.61 134.76±8.62Table 4. Maintenance of long-term potentiation (LTP) in the hippocampal dentate gyruspost-injury. Normalized slope values (mean ± SEM) measured at 10, 60, 120, and 180 minfollowing theta burst stimulation (TBS). Measurements were recorded one-week post-injuryin sham and FPI rats treated with vehicle (DMSO), a TLR4 inhibitor (TAK-242), or an MMP-9inhibitor (SB-3CT). ### Page 17 TABLE 5:Day1 Day2 Day3Groupn(rats)Latency(seconds)Distance(meters)Latency(seconds)Distance(meters)Latency(seconds)Distance(meters)SHAMDMSO 10 61.36±11.11 3.32±0.87 49.19±9.30 2.83±0.36 41.18±10.78 3.17±1.00FPIDMSO 10 113.1±16.68 7.20±1.67 87.06±10.64 9.07±1.72 50.21±10.34 5.39±1.80SHAMTAK-242 7 69.30±19.92 3.14±0.58 82.90±25.52 6.06±1.41 67.74±21.15 4.84±1.01FPITAK-242 7 102.2±24.2 5.25±1.10 40.26±11.01 2.76±0.46 58.04±16.63 3.53±1.18SHAMSB-3CT 6 82.58±24.05 10.4±2.30 42.12±10.34 3.00±0.84 62.50±6.84 4.68±0.89FPISB-3CT 7 67.86±18.33 5.43±2.67 46.66±4.97 3.46±0.40 51.73±22.18 4.51±2.29Table 5. Spatial memory performance in the Barnes maze task one month after braininjury. Mean latency (seconds) to reach the escape hole and total distance traveled(meters) by sham and FPI rats on training days 1–3. Testing was conducted one-monthpost-injury and values are given as mean ± SEM. Treatment groups received vehicle(DMSO), TLR4 inhibitor (TAK-242), or MMP-9 inhibitor (SB-3CT) immediately following injury.